Information

2.2: Weaker Bonds in Biology - Biology

2.2: Weaker Bonds in Biology - Biology


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Learning Objectives

  • Model a Hydrogen bond and identify its unique qualities
  • Model van der Waals interactions identify their unique qualities

Hydrogen Bonds

Ionic and covalent bonds between elements require energy to break. Iconic bonds are not as strong as covalent, which determines their behavior in biological systems. However, not all bonds are ionic or covalent bonds. Weaker bonds can also form between molecules. Two weak bonds that occur frequently are hydrogen bonds and van der Waals interactions. Without these two types of bonds, life as we know it would not exist. Hydrogen bonds provide many of the critical, life-sustaining properties of water and also stabilize the structures of proteins and DNA, the building block of cells.

When polar covalent bonds containing hydrogen form, the hydrogen in that bond has a slightly positive charge because hydrogen’s electron is pulled more strongly toward the other element and away from the hydrogen. Because the hydrogen is slightly positive, it will be attracted to neighboring negative charges. When this happens, a weak interaction occurs between the δ+ of the hydrogen from one molecule and the δ– charge on the more electronegative atoms of another molecule, usually oxygen or nitrogen, or within the same molecule.

Try It

This interaction is called a hydrogen bond. This type of bond is common and occurs regularly between water molecules. Individual hydrogen bonds are weak and easily broken; however, they occur in very large numbers in water and in organic polymers, creating a major force in combination. Hydrogen bonds are also responsible for zipping together the DNA double helix.

Learning Objectives

A YouTube element has been excluded from this version of the text. You can view it online here: pb.libretexts.org/bionm1/?p=100

Van der Waals Interactions

Like hydrogen bonds, van der Waals interactions are weak attractions or interactions between molecules. They are also called inter-molecular forces. They occur between polar, covalently bound atoms in different molecules. Some of these weak attractions are caused by temporary partial charges formed when electrons move around a nucleus. These weak interactions between molecules are important in biological systems and occur based on physical proximity.

Try It

Have you or anyone you know ever had a magnetic resonance imaging (MRI) scan, a mammogram, or an X-ray? These tests produce images of your soft tissues and organs (as with an MRI or mammogram) or your bones (as happens in an X-ray) by using either radiowaves or special isotopes (radiolabeled or fluorescently labeled) that are ingested or injected into the body. These tests provide data for disease diagnoses by creating images of your organs or skeletal system.

MRI imaging works by subjecting hydrogen nuclei, which are abundant in the water in soft tissues, to fluctuating magnetic fields, which cause them to emit their own magnetic field. This signal is then read by sensors in the machine and interpreted by a computer to form a detailed image.

Some radiography technologists and technicians specialize in computed tomography, MRI, and mammography. They produce films or images of the body that help medical professionals examine and diagnose. Radiologists work directly with patients, explaining machinery, preparing them for exams, and ensuring that their body or body parts are positioned correctly to produce the needed images. Physicians or radiologists then analyze the test results.

Radiography technicians can work in hospitals, doctors’ offices, or specialized imaging centers. Training to become a radiography technician happens at hospitals, colleges, and universities that offer certificates, associate’s degrees, or bachelor’s degrees in radiography.


2.2: Weaker Bonds in Biology - Biology

Ionic and covalent bonds between elements require energy to break. Iconic bonds are not as strong as covalent, which determines their behavior in biological systems. However, not all bonds are ionic or covalent bonds. Weaker bonds can also form between molecules. Two weak bonds that occur frequently are hydrogen bonds and van der Waals interactions. Without these two types of bonds, life as we know it would not exist. Hydrogen bonds provide many of the critical, life-sustaining properties of water and also stabilize the structures of proteins and DNA, the building block of cells.

When polar covalent bonds containing hydrogen form, the hydrogen in that bond has a slightly positive charge because hydrogen’s electron is pulled more strongly toward the other element and away from the hydrogen. Because the hydrogen is slightly positive, it will be attracted to neighboring negative charges. When this happens, a weak interaction occurs between the δ+ of the hydrogen from one molecule and the δ– charge on the more electronegative atoms of another molecule, usually oxygen or nitrogen, or within the same molecule. This interaction is called a hydrogen bond. This type of bond is common and occurs regularly between water molecules. Individual hydrogen bonds are weak and easily broken however, they occur in very large numbers in water and in organic polymers, creating a major force in combination. Hydrogen bonds are also responsible for zipping together the DNA double helix.


Epitaxy of Small Organic Molecules

12.2.2 Organic–Organic Small-Molecule Interfaces

Organic–organic heteroepitaxial interfaces in thin films are a subset of the broader class of interfaces between molecular solids with different crystal structures. Compared with inorganic epitaxial materials, organic solids have relatively weak bonds , thus do not in general form the coherent, highly strained structures that are commonplace in the heteroepitaxy of semiconductors and complex oxides. Instead, the formation of organic–organic interfaces is dominated by the creation of energetically favorable arrangements of the molecules at the interface. The concepts relevant to the creation of favorable interfaces have been reviewed by Hooks et al., who have divided interfaces into systems that are linearly or axially commensurate and systems that exhibit quasiepitaxy [62] . Hooks et al. describe the relationship between the vectors a1 and a2 describing the two-dimensional (2D) lattice on one side of the interface and the vectors b1 and b2 on the opposite side. A matrix of coefficients relates the two sets of lattice vectors such that: [62]

When p, q, r, and s are all integers, the lattices on the two sides are commensurate with integer multiple unit cells. If p, q, r, and s are rational numbers, the lattice has a more complex coincidence structure. For irrational values of the matrix coefficients, the interface is incommensurate, and exhibits a preferred orientation but lacks a lattice of coincident sites. The geometries of a very large numbers of interfaces have been reported [3,62] and it has been found that the preferred epitaxial arrangement can be predicted using geometric considerations [94] . The interface potential can be parameterized by considering the interaction across the interface and explored using Monte Carlo techniques to generate likely interface structures [95] .

Incommensurate interfaces between organic molecular crystals can include long-period structures organized over distances corresponding to many molecular sizes. A characteristic incommensurate structure with a period of approximately 8 nm is observed at a pentacene/C60 interface where a pentacene monolayer is grown on C60 [96] . The long-period structure forms along specific in-plane orientations and is attributed to buckling in the pentacene monolayer [96] . The incommensurate order can also result in the formation of crystals with anisotropic shapes driven by a more favorable match along specific in-plane directions. Thin layers of quaterrylene on potassium hydrogen phthalate form 1D crystals driven by the establishment of a preferred incommensurate interface orientation [97] .


Lecture 3: Biochemistry 2

Download the track from iTunes U or the Internet Archive.

Topics covered: Biochemistry 2

Instructors: Prof. Robert A. Weinberg

Lecture 10: Molecular Biolo.

Lecture 11: Molecular Biolo.

Lecture 12: Molecular Biolo.

Lecture 13: Gene Regulation

Lecture 14: Protein Localiz.

Lecture 15: Recombinant DNA 1

Lecture 16: Recombinant DNA 2

Lecture 17: Recombinant DNA 3

Lecture 18: Recombinant DNA 4

Lecture 19: Cell Cycle/Sign.

Lecture 26: Nervous System 1

Lecture 27: Nervous System 2

Lecture 28: Nervous System 3

Lecture 29: Stem Cells/Clon.

Lecture 30: Stem Cells/Clon.

Lecture 31: Molecular Medic.

Lecture 32: Molecular Evolu.

Lecture 33: Molecular Medic.

Lecture 34: Human Polymorph.

Lecture 35: Human Polymorph.

Good morning, class. Nice to see you again. Hope you had a great weekend. If you didn't, it wasn't because of the weather.

So here I am, once again a member of the walking wounded, and we're talking about carbohydrates today, as you may recall, or at least we were at the end of our discussion last time.

And, we made the point that these multiple hydroxyl groups on the carbohydrates, on the one hand, determine the identity of various kinds of sugars.

Just the orientation, the three-dimensional orientation of them, for one thing, and for another that these multiple hydroxyl groups represent the opportunity for forming covalent bonds with other monosaccharides as is indicated here in these disaccharides, or covalent bonds end-to-end to create large molecules, which will increasingly be the theme of our discussion today, i.e. when I talk about large molecules, we just used the phrase generically, macromolecules, since in principle these end to end joinings of molecules which involve the dehydration and the formation of these covalent bonds like right here can create molecules that are hundreds, indeed even thousands of subunits long.

So, here, if we're talking about a polymer, we refer to each one of these subunits of the polymer as being a monomer, and the aggregate as a whole as being a polymer.

Here, we touched upon the fact toward the end of last lecture, in fact, at the very end, that one can cross-link these long, linear chains of carbohydrates.

And here, we see the fact that glycogen, which is a form of glucose that is stored in our liver largely, and to a small extent in the muscles actually is cross-branched. So, if one draws on a much smaller scale a glycogen molecule, one might draw a picture that looks like this.

And it looks almost like a Christmas tree with multiple branches.

And, the purpose of this is actually to sequester the glucose, to store the glucose into metabolically inactive form until the time comes that the organism needs, once again, the energy that is stored in the glucose upon which occasion these bonds are rapidly broken down and the glucose is mobilized and put into the circulation for eventual disposition and use in certain, specific tissues.

While it's encumbered in these high molecular weight polymers, the glucose is essentially metabolically inactive.

The body doesn't realize it's there.

And, we can, as a consequence store large amounts of energy in these glycogen molecules.

And it can be stored there indefinitely.

Now, the fact is this idea of end-to-end polymerization that I just mentioned can be extended to other macromolecules which also become linked end-to-end in specific kinds of polymers.

And here, we are moving, now, into the notion of talking about amino acids.

And, we're talking about proteins.

If we look at an amino acid, what we see is it has an important structure like this.

Here's a central carbon ? for, in principle, the distinct side chains where R represents some side chain that can be any one of, as we'll see shortly, 20 distinct identities.

But, all the amino acids share in common the property that they have this overall structure.

And, as you may recall from our discussions of last week, at neutral pH, an amino acid of this sort, whatever R is, wouldn't look like this at all because the amine group would attract an extra proton, causing it to become positively charged.

And, the carboxyl group would release a proton, causing it to become negatively charged.

And, as you might deduce from this, at very low pHn due to the greatly increased concentration of protons, free protons in the solution, the equilibrium would be driven more in favor of reattaching a proton to the carboxyl group just because there are so many of these protons around.

Conversely, at very high pH, where the hydroxyl ions are in predominance, they obviously tend to scavenge protons, reducing the level of protons to very low levels in the water.

And, under very high pH conditions, this proton would be released and pulled away by the hydroxyl ions causing this amine group once again to return to its negative charge state.

Now, the fact of the matter is that these amino acids exist in a very specific three-dimensional configuration.

And that's illustrated much more nicely here than I could possibly draw on the board, which in any case would be hopeless.

And, you can see the principle that once you have four distinct side groups coming off of carbon, that there is, in principle, two different ways to create them.

And, this is sometimes called chirality.

Chiral, you see, is the form right here.

If I try, as much as I will, to superimpose one hand on top of another.

It doesn't work because they are mirror images of one another, which are asymmetrical.

And, as a consequence, we see a similar kind of relationship occurring here where we see that these two forms of amino acids could, in principle, exist.

And, they are not interchangeable unless one breaks one of the bonds and reforms it.

These two forms are called the L and the D, and it turns out that the L form is the one that's used by virtually all life forms on the planet, i.e. there was an arbitrary choice made sometime about 3 billion years ago or more to use one of the three dimensional configurations, and not to use the other.

The other is found in certain rare exceptions, but virtually all life forms on this planet use the L form.

That said, by the way, this indicates some of the arbitrary decisions that were made early during evolution because we could imagine on another planet if life were to exist there and it were to depend on amino acids, and that evolutionary system might have chosen the D form.

So, this is sort of a luck of the draw.

This is actually the way things evolved here.

And, what we begin to see, now, is if we talk about proteins or if we wanted to be more specific and use the more biochemical term ?polypeptide,? we see once again we have an end-to-end joining system which is a bit different from that which the monosaccharides employ to create long chains of glycogen or of starch because here we see once again a dehydration reaction where an amine group and a carboxyl group are caused to shed their hydroxyl and the proton, causing the formation of a peptide bond.

And here, we see this important, very important biochemical entity, a peptide bond consisting here of this carbonyl and this nitrogen fused in this specific way.

And, of course, if you recognize this as being a peptide bond, then you can understand why proteins are sometimes given the term ?polypeptide.?

In some cases, if one has very short stretches of amino acids linked end to end like this, we talk about these being oligopeptides, where ?oligo? is the general term used in biology to refer to a small number of things rather than a large number of things.

And, once again, we have, here, the possibility of extending this infinitely. There are no constraints, in principle, on making this 500, 1,000, even 2,000 amino acids long, where each one of these, once again, is an amino acid, and where once again I'm being very coy about the identities of R1 and R2, which, as I will indicate very shortly, can be one of 20 distinct alternatives.

Here, you see that we are continuing this process of peptide bond formation.

And most importantly here is the realization that there is a polarity of elongation here.

It doesn't move with equal probability left or right, or right to left.

We start at the amino end here.

This is the amino end, and this is the carboxyl end.

The amino end and the carboxyl end, and invariably, again because of the way life has evolved on this planet, the new amino acid is added on the carboxyl end.

And so, when one often talks about proteins, one refers to their N terminal, and to their C terminal ends, these referring obviously to the amino group at one end and a carboxyl and at the other end so that polarity is always a directed synthesis adding it on C-terminal end, in other words to use a short-hand notation, we think about proteins as going with this polarity N toward C.

Things are growing at the C terminal end progressively.

And, each time one can imagine the addition of an amino acid on the end of it.

So, again, it can be extended, in principle, indefinitely.

Keep in mind as well, something that's implicit in everything I'm telling you but I won't always mention it explicitly, and that is virtually every biochemical reaction is reversible.

And therefore, if one is able to form a peptide bond, one is able to break it down by biological means as well, i.e. by introducing a water molecule back in and thereby using the process of hydrolysis, which is the breakdown of a bond through the introduction of a water molecule to destroy the previously created bond.

To use an MIT phrase, the reversibility is intuitively obvious because if you are able to make a, well, I don't know if it?s still used, but it was used in the late Stone Age around here.

Anyhow, any biochemical action must be reversible because if, for example, this polymerization were irreversible, then all the protein that was ever synthesized on the surface of the planet over the last 3 1/2 billion years would accumulate progressively.

And obviously, that doesn't happen.

And therefore, macromolecular synthesis, to the extent that it proceeds forward, obviously must go the other direction as well.

And the resulting concentration of a complete protein is known as its steady state.

So we might make a protein at one rate and break it down at the same rate.

And its steady-state concentration represents the compromise between these two, i.e., the concentration of such a protein that we might observe at any one point in time.

Indeed, the term ?steady-state? could be expanded to any process in which there is a synthesis and there is a breakdown of something.

And the equilibrium concentration which results is, once again, called the steady-state of that molecule. Now, let's get down to the nitty-gritty, which is obviously something which we can't avoid for very long, which is to say the R's, i.e. the side chains.

Once again, here we see an arbitrary artifact of very early evolution in the biosphere because there are, in effect, 20 different side chains creating 20 distinct amino acids, which are used in proteins by all organisms on this planet.

Again, there are rare exceptions, certain fungi and certain bacteria are able to make unusual amino acids.

But these are the basic building blocks of virtually all life forms on the planet. 99.99% of all the protein that is created is synthesized through the polymerization of these 20 amino acids.

And, by the way, one of the amino acids, glycine, over here, you see it right here, violates this rule of chirality.

And, you will recall before I said that because there are four distinct amino acids, four distinct side chains around a central carbon sometimes called the alpha carbon, you always have a handedness of amino acids.

But this notion cannot be respected in the case of glycine seen up here simply because we don't have four distinct, here's the central carbon where I'm pointing with the red, and here these two hydrogens are equivalent to one another.

They are not four distinct chains.

There's only three distinct chains here.

So glycine violates this rule of chirality, of left- and right-handedness. And here, by the way, the side chain, which in all of these cases is depicted as extending off to the right of each amino acid, the side chain is simply an H, simply a proton, a hydrogen atom.

In fact, what we see about these amino acids is that the side chains have quite distinct biochemical properties.

And that begins to impress us with the notion that proteins and their biochemical attributes can be dictated by the identities of the amino acids that are used to construct them.

We can talk about the notion of nonpolar versus polar amino acids, i.e., amino acids which have poor affinity for water.

They don't have a separation of plus and minus charges.

And as a consequence, they are a little bit or quite a bit hydrophobic.

Now, you will say, well, how can they be hydrophobic, because here this oxygen is charged, and here this amine group is charged? That would make it highly hydrophilic.

But keep in mind, when I'm talking about these amino acids, I'm not talking about them when they are in a single amino acid form.

I'm talking about their properties once they have been polymerized into state like this.

And, once they are polymerized into state like this, the NH2 and CO charging, that is, the charge here and the charge here become irrelevant because this oxygen and this amine group are both tied up in covalent bonds.

And, this acquisition of a proton and this shedding of a proton over here cannot occur, because both of these atoms, O and N, are involved in covalent bonds.

So therefore, when we talk about nonpolar and polar amino acids, keep in mind we are focusing on the biochemical properties of the side chain because the central backbone of the polypeptide and the central backbone is defined quite clearly here.

Here's the central backbone, and you see it has a quite repeating structure, N, C, C, N, C, C, N, C, C, this is invariant.

What changes, and what defines the biochemical attributes of this oligopeptide, or a polypeptide, are the identities of these side chains, which again are plotted on this particular graph.

You have a different version in your book off to the right.

Here, you see, we have a proton, a methyl group, a valine, a lucine, an isolucine, and the differences between this suggests these are all quite aliphatic, quite similar to the propane that we talked about last time, or the hexane.

That is to say, these are quite hydrophobic side groups.

And, as such, if there were a polypeptide, we can imagine, and you put the polypeptide in water, you can imagine that these amino acids would not like to be directly confronting the water because of the fact that they are hydrophobic.

Methionine is also a bit hydrophobic.

I'm equivocating there because the S has a slight degree of hydrophilicity.

It has a slight degree of polarity, but not really that much.

And, these aromatic side chains here, because they have these benzene rings, consequently are called aromatic.

These are quite strongly hydrophobic.

So, they really hate to be in the intimate contact with water.

Here, on the other hand, let's look at these side chains because here we have strongly polar molecules, side chains again.

Keep in mind we are focusing on the side chains.

Here we see serine with the hydroxyl group that can form hydrogen bonds with the water, threonine, which has its own hydroxyl group, asparagine, which has two atoms here, this carbonyl and the NH2, both of which can form hydrogen bonds with the water, as can glutamine.

So, these are quite hydrophilic.

They are not as fanatically hydrophilic as these charge molecules where the side chains are not just capable of forming hydrogen bonds.

In this lower group here, the side chains are capable of undergoing ionization.

So they're actually strongly charged.

And here, we see here the carboxyl group, and our aspartic acid and glutamic acid has actually discharged its proton, becoming negatively charged.

These are acidic amino acids, by virtue of the carboxyl group they have, basic amino acids here: arginine, lysine, and histidine, all acquire a positively charged side chain by virtue of these nitrogen here which have a strong affinity for pulling away protons or abstracting protons from the aqueous solvent.

And so, we have a whole gradient of hydrophilicity down to hydrophobicity.

And here, we have intermediate structures.

We also have some very special idiosyncratic kinds of amino acids.

Here is tyrosine, and tyrosine is little bit schizophrenic again.

It has this highly hydrophobic aromatic group here, the benzene ring, which hates to be in water, and the hydroxyl group which actually is a friend of water.

So, here, we have something where its role is quite equivocal.

Here, we have cystine, as indicated here, and what's interesting about the cystine group in this case is the SH group, the side chain, the SH group, because this SH group is able to form bonds with yet other SH groups from other cystines.

So, let's just look at the cystine here for a moment.

You see there's a CH2, and then there's an SH.

So, let's imagine, I'm not going to draw all the atoms here, but let's imagine here we have the CH2 group.

I'm not drawing the backbone, SH, over here.

And, we can imagine another protein chain, another polypeptide chain down here.

Again, I'm not drawing the backbone, but I'm drawing another SH like this.

And, the fact is, under the conditions of oxidation and reduction that operate at least in the extracellular space, one can oxidize this, these two, resulting in the formation of what is known as a disulfide bond.

So, here, we have now for the first notion the idea that the polypeptide chains can be covalently linked to one another through these cross-links, as indicated here.

Conversely, if you add a reducing agent that will add protons back to this, and reduce the oxidation state of the sulfurs, once again causing the disulfide bond to fall apart.

Now, in principle, these disulfide bonds could be used to link two proteins together.

But, more often than not, if you look at the structure of a single protein, here's the structure of a single protein.

And often, there are intramolecular bonds, disulfide bonds, i.e., bonds from one domain of the protein to another, from one part of the protein to the other.

I'll draw them in right here.

Here might be a disulfide bond.

Here might be a disulfide bond, and I could go on and on.

There might be another one over here.

Why do we have these disulfide bonds? Because as we will indicate very shortly, the three-dimensional structure of a protein is very specifically determined.

A protein can only function when it assumes a certain three-dimensional configuration, when it assumes a certain three-dimensional, stereochemical configuration.

When we talk about stereochemistry, we are talking about the three-dimensional structures of molecules, small and large.

And, here, we begin to touch on a theme of how these complex polypeptide chains are able to create proteins that have very specific, often very rigid, structures in three-dimensional space.

Part of this structural rigidity is maintained by these covalent disulfide bonds, which tightly link neighboring regions, or even not so neighboring regions, of a single polypeptide chain, these intramolecular links.

This doesn't preclude there being intermolecular links between two polypeptide chains that are mediated as well by the disulfide bonds.

Here's another very peculiar amino acid because what you see here is at the side chain, which is CH2, CH2, CH2, CH2 is hydrogen bonded here to the amine group.

It's not swinging out in free space.

What we see here is CH2, CH2 is covalent bonded to the amine group.

You pick that up, right? I was just testing you.

OK, so here we see a five-membered ring that's created.

So here, this thing is not swinging out in free space.

It creates a five-membered ring where the end of the side chain is actually covalently linked to the amino group.

And, that also has implications for the structure of proteins because this particular amino acid, whenever it occurs within a polypeptide chain, doesn't have the flexibility of assuming certain configurations that the other ones have whose four side chains are not so encumbered.

None of them has total flexibility, but this one is far more encumbered in the kinds of three-dimensional structures that it can assume.

And, with that in mind, we begin to ask questions about how polypeptide chains assume three-dimensional structure.

If we talk about a polypeptide chain, in our minds, hopefully, there's only 28 combinations.

Oh, am I good or what? Anyhow, all right, so, look here.

And here, you see, this is a typical polypeptide chain.

Here, we have a three letter code.

In truth, there is a single letter code which was introduced around 1965. So, each of the 20 amino acids has its own single letter code.

And, to make a frank and depressing admission, 35 years, 40 years after the single amino acid letter code was instituted, I still haven't learned it.

But, we could learn these three letter codes, which fortunately are present here.

In the single letter code L is lucine, and A is alanine, see, they know it.

This is another example of not being able to teach old dogs new tricks.

Anyhow, so here we see the way, one way by which one might depict an amino acid chain, a polypeptide chain.

And keep in mind, this can go on indefinitely.

As we begin to wrestle with the three-dimensional structure of the chain, we begin to realize the following, and that is that after the chain is initially synthesized, it's initially chaotic.

And, as it extends, it increasingly begins to assume a very specific three-dimensional molecular configuration which is indicated down here.

So, the chaos that operates initially will eventually result in a native configuration over here, which in many respects often represents the lowest free energy state.

Since for the last 40 years, people have been trying to figure out, if you knew the amino acid sequence of this primary polypeptide here, if you knew its primary structure, and when I say, ?primary structure,? what I mean is the sequence of the amino acids.

So, if you knew the primary structure of the amino acids, you should, in principle, be able to develop a computer algorithm that would predict the three-dimensional configuration, which is shown here in a very schematic way, and which we will discuss in much greater detail shortly.

And, the fact is, after 40 years of trying, one still is unable to do that, i.e., if I were to give the primary amino acid sequence of the polypeptide to the smartest biochemists in the world, and there are some very smart ones, he or she could still not tell me what the three-dimensional structure of this protein with total certainty would be.

Why? Because there's an almost infinite number of intramolecular interactions that greatly complicate how the protein assumes the structure.

Moreover, if we talk about this as the native state of the protein, we can imagine that there?s ways of disrupting that because much of this native state is created by intramolecular hydrogen bonds.

Remember, the hydrogen bonds are relatively weak, and if we heat up the temperature, then we can break hydrogen bonds.

And therefore, every time we fry an egg, for example, if we want to get down to Earth, we denature. We break up the native three-dimensional structure of the albumin molecules that constitute the egg white.

And so, when everything turns white, what we've done is to take a native molecule like this, heated it up to temperatures where the intramolecular bonds no longer stabilize.

Notably, hydrogen bonds no longer stabilize this three-dimensional configuration, and we put it into a denatured state, which might be all the way up here.

And, therefore, this acquisition of a native configuration, or a native state, native representing the natural state, is also reversible in many molecules simply by heating them up.

There are to be sure yet other molecules which are different from the egg white from the albumin in egg white where if you cool them back down, they will spontaneously reassume their native structure.

Many proteins, most, will not do so.

Well, again, let's go back to this issue of the acquisition of complex, three-dimensional structure.

And here, we begin to see how some of this structure is acquired and stabilized through these intramolecular hydrogen bonds. And there are many opportunities for these intramolecular hydrogen bonds because here we see one polypeptide chain here, here we see another.

And, we see that the NH2 group right here, I'm sorry, the nitrogen group here with the proton side chain, and the carbonyl group here with the oxygen are not encumbered.

They are, in principle, available to form hydrogen bonds with a polypeptide chain somewhere else.

Now, this other polypeptide chain could once again be from another protein, from another polypeptide.

But more often than not, we are once again dealing with intramolecular cross-links. But in this case, the intramolecular cross-links are not disulfide bonds which are covalent, and hard and stable as a rock in the absence of reducing agents.

Here, we're talking about much weaker bonds, hydrogen bonds which also act between different loops of the protein and serve, once again, to stabilize the three-dimensional structure, the native state of the protein.

And, you can see how these opportunities for forming multiple hydrogen bonds can create an enormous degree of stability.

And, here are some examples of what we now call the secondary structure of the protein.

Just a second ago, or several minutes ago to be honest, and I'm always honest with you, class, the primary structure is the amino acid sequence.

The secondary structure represents configurations like this.

Here is a beta pleated sheet.

And, what we see here in this alpha helix is we have a helical structure where the amine group down here, the NH group, hydrogen bonds with a residue that is, I think, three and a half residues upstream, one, two, there's an amine down there, so, with the carbonyl group that's three and a half residues upstream of it.

This one, once again, reaches three and a half residues upstream.

Not all the hydrogen bonds are shown in the background.

Only the ones on our side of the helix are shown, on the front side of the helix.

But, you can imagine that this can perpetuate itself.

And, each of these carbonyl's may associate with a proton, an NH group that's either above or below that particular residue.

And this, in turn, can create a helical structure.

By the way, proline doesn't fit well.

If you add a proline in here, proline is known in the trade as a helix breaker.

Why? Because it cannot twist itself around to form an alpha helix.

And so, if the primary amino acid were to dictate that a proline would be inserted right here, for example, then this helix might exist down below and above, but it would not be continuous because the presence of a proline is highly disruptive of the formation of an alpha helix.

This means that, in principle, you can make some predictions about the localized structure of a polypeptide by knowing whether or not proline is present, for example.

But that still doesn't give you the power to predict the entire three-dimensional structure of the finished protein itself.

Now, let's agree that this is the secondary structure of the protein, i.e., the various domains which often form alpha helices within a certain segment of the protein or a certain segment of the protein will form beta pleated sheets.

And there are several other less common kinds of secondary structure.

And here, we deal with tertiary structure.

Now we are getting really interesting.

Or, maybe you don't like it.

But some people say it's really interesting because here are the tertiary structures of some arbitrarily chosen proteins.

Here, the tertiary structure of this particular protein, and the identities of these are not given in our textbook.

And, I'm sure if we spent two or three weeks, we could find out what they were.

But anyhow, here is a protein, a three-dimensional structure of a protein which is composed of four alpha helices which go up.

Another alpha helix, alpha helix, alpha helix, alpha helix, they are depicted here, fortunately, in four different colors.

And so, we see that what we talk about tertiary structure, we're talking about how the alpha helices are disposed with respect to one another.

The primary structure of the amino acid sequence is not shown here.

The secondary structure represents these individual alpha helices, and the tertiary structure represents how these alpha helices are arranged vis-?-vis one another.

Here is a protein which is structured much differently.

It's formed of many beta pleated sheets.

We saw that in the last figure, in the last overhead.

You see it as a quite different overall three-dimensional structure.

This could be the beginning of an alpha helix down here, although that's quite equivocal.

And here, we see yet another point.

And that is, as we said before, the tertiary structure independent of these alpha helices and beta pleated sheets may be stabilized by these covalent inter-strand cross-links formed by the cystines.

And in the end, if we put all that together, then we come to the realization that the three-dimensional structure of a protein as determined by the art of x-ray -- There we go.

I actually have a cousin who I won't mention whose son was so dyslexic that when he came to stairways he didn't know whether to put his foot up or down.

OK, anyhow, because I solved it within less than two minutes time, all right, so here we see this is what the three-dimensional structure of a protein looks like.

This is called a space-filling model because here, one draws in, as determined by x-ray crystallography what the, if we could see what a protein looks like, what it actually must look like, where each of the atoms including these side chains is actually depicted.

Before, when we used these far more schematic descriptions like here, we were just talking about the overall structure of the backbone.

We weren't really indicating where the side chains were, and what space they would fill up.

And, if we give them the chance, if we put in all of the other atoms, the side chains, and we create a space-filling model where the actual atoms are shown, this is what the protein would look like.

And the fact of the matter is that all virtually proteins have very specific structures.

It's not as if they can shift from one structure to another.

Once they leave their normal native structure they will lose their ability to do what their normal jobs are.

And, this particular overhead happens to bring in yet another theme that we're going to focus on increasingly, which is, what do proteins do in cells? I'm glad I asked that question.

One of the things they do is they act as catalysts, i.e. , as enzymes.

The fact is, as we will discuss later, virtually all biochemical reactions require an enzyme catalyst in order to propel them forward.

That is to say, if there's a biochemical reaction to occur, almost always it will not occur spontaneously the same way that a hydroxyl ion and a hydrogen will join together spontaneously in water.

Almost all biochemical reactions require the mediation of an enzyme which is a biological catalyst in order to encourage this to happen.

And, almost all catalysts in our cells are proteins.

So, if you have 4,326 distinct biochemical reactions occurring in the cell, that means that there's probably almost as many distinct enzymes, each one of which is assigned to mediate one or another of those distinct biochemical reactions.

And here, we see the fact that this is an enzyme which happens to be called hexokinase.

Recall that the -ase suffix at the end dictates that this is already an enzyme rather than a carbohydrate.

And, this attaches, in fact, a phosphate group onto glucose.

And, what happens is that the glucose, which is the substrate, which is acted upon by the catalyst, is pulled into this site in the protein which is highly specialized to mediate the enzymatic reaction.

Almost all the business of this complex enzyme is carried out right here.

And somehow, a lot of the other amino acids that are located at a distance are doing other things like regulating the activity of the enzyme.

But the actual business end of the enzyme is present in what is called a catalytic cleft, an active site of this enzyme in which the substrates are pulled in and are manipulated and changed chemically by the actions of this particular enzyme.

Now, in saying that virtually all catalysts, but not all, are proteins, I also mean to say that proteins have a second major function in the body.

The first major function is to act as enzymes in catalysts.

The second major function is to create biochemical structures, i.e., structures of different cytoskeleton proteins such as I showed you two lectures ago.

And so, we are going to come repeatedly to the situations where complex structural entities in the cell are composed of different structural proteins.

Again, this is just a prelude to talking about these in greater details, these two major functions of enzymatic catalysis on the one hand, and creating structure on the other hand. And so now, we get to really four hierarchical levels of protein structure.

The primary structure is the amino acid sequence.

And, if we dwell for second on this amino acid sequence, let's realize that any single amino acid can follow any other amino acid.

So, what that means is that if glycine is the first amino acid, as it happens to be here, serine is only one of 20 different possible second amino acids.

Aspartic acid is only one of 20 different third amino acids as the third residue.

We often call these different residues: the first residue, second residue, third residue, fourth residue, and fourth, and so forth.

And, keep in mind, if we think about the combinatorial implications of that, the first amino acid residue can have 20 different ones.

The second can have 20 different identities.

The third can have 20 different identities.

That means if we make a tripeptide - a tripeptide has three amino acids in it.

That means we can make 400 dipeptides, 400 distinct dipeptides, and we can make 8,000 distinct tripeptides.

Now, if you imagine that the average amino acid, the average protein in the cell is, let's say, 150 amino acid residues long, that means that in principle, one could make 20 to the 150th power distinct amino acid sequences because of these absence of any constraints of which amino acid will follow which other amino acids. In other words, if the average polypeptide has this many residues, this is the number of distinct 150 amino acid residue long proteins that one could, in principle, synthesize.

I'm not saying all of them have ever been synthesized since the formation of life on this planet.

Indeed, since some amino acid chains are 4, 5, 600, even 2,000 amino acid residues long, I think the one that is affecting muscular dystrophy is more than 2,000 amino acids.

Dystrophin. Does anybody know here? It's big.

Anyhow, imagine the number of possibilities.

So, combinatorially, life can make almost whatever types of amino acids it would like by dictating the sequence of amino acids.

Now, let's just go and look here again.

There is a secondary structure.

The tertiary structure is the way in which the different alpha helices here or beta pleated sheets are disposed three-dimensionally with respect to one another.

And, the quaternary structure represents how different polypeptides are associated one with the other.

So, for example, hemoglobin is a tetramer.

Hemoglobin doesn't exist as a monomeric protein.

Its solution exists as a tetramer.

And there's two kinds of globin chains.

There is an alpha kind and a beta kind.

And, if we look in a very rough and schematic way at the way that a hemoglobin tetramer is arranged, there are two alpha polypeptide chains and two beta polypeptide chains.

They are not covalently attached to one another.

They are associated with one another via hydrogen bonds and hydrophobic interactions.

And, this is the actual native configuration of globin to alpha and to beta chains.

It doesn't exist as a single amino acid in solution.

And, indeed, most, or I shouldn't say most, but very many proteins exist in these configurations where the tertiary structure represents four different amino acid chains.

And each of these has an N and C terminal.

Each of these is chemically distinct.

These four could probably be taken apart from one another simply by raising the temperature.

And, they associate like this.

And, in the absence of this association, if you just had one of these alphas, or one of these betas, it wouldn't function well at all.

In fact, it might be totally dysfunctional.

One other thing that may be implicit to you, but I haven't said, but that is very important to realize is the following: Let's imagine that this is the three-dimensional structure of the protein, as it may well be.

Let's now think about hydrophobic and hydrophilic amino acids.

The hydrophobic amino acids hate to be present water.

And therefore, they are, we can imagine this case correctly, tucked away inside the interstices of the protein far way from the surface.

They don't have any contact with water.

Conversely, the highly charged hydrophilic amino acids are actually sticking out at the surface.

And this begins to yield yet another insight into how the three-dimensional stereochemistry of proteins is maintained and dictated because the hydrophobic amino acids, through hydrophobic interactions, stabilize the inner core of the protein that is well shielded from the aqueous solvent.

The hydrophilic amino acids are on the outside.

They like to be in intimate contact with the water.

So, we already now have talked about a number of distinct different interactions that are responsible for creating the three-dimensional stereochemistry of the protein.

First of all, there are the disulfide bonds, which create chain-to-chain covalent interactions.

They are the hydrogen bonds in which different chains can interact one another.

And there are these hydrophobic and hydrophilic interactions.

And, there are some relatively inconsequential van der Waals interactions, which are really not worth discussing although some people get really excited about them.

So, here we now begin to see that we have really interesting polypeptides unlike the boring polypeptides that are ultimately the way one must judge carbohydrates.

Some people think carbohydrate chemistry is really interesting.

But it really isn't that interesting because you just have the same monomer in a hundred, or 500 stretches.

Here, a protein is much more interesting because of this enormous variability in amino acid sequence, and the consequent ability to create all kinds of chemical reactivities and structures because of these 20 different amino acids.

If we were to imagine life on another planet, and we imagine that there were, let's say, amino acid-like molecules that were part of life, maybe that other life wouldn't have exactly the same 20 amino acids as we do.

It almost certainly would be a water base the way we are.

But, it would also rely on hydrogen bonds and hydrophilicity, and hydrophobicity interactions in order to dictate the three-dimensional structure.

In the absence of this very specific three-dimensional structure I will tell you that this enzyme could not function.

And, if you were to take this enzyme, if it were typical enzyme and you were to heat it up briefly, even often slightly above normal body temperature, it might denature, i.e., it might lose its three-dimensional structure irreversibly.

And, once it was denatured, this process of denaturation, it might not be able to spontaneously reassume that pre-existing three-dimensional configuration and therefore would forever be inactive.

That means to say very explicitly that even though the amino acids that are creating that active catalytic site remain there.

Their highly specific three-dimensional disposition is critical for the continued actions of this enzyme.

And, once their three-dimensional dispositions are shifted around through the process of interactions, then, we have trouble because the enzyme can no longer do its assigned task.

We are going to go now to an even higher order of complexity in one sense.

We are going to go to the royalty of the macromolecules, which are the nucleic acids.

Of course, protein chemists would take great umbrage at the very notion that there are things better than proteins.

But, the fact of the matter is, I can't show you that overhead because it's from the other textbook which is copyright, and we are being filmed.

How many people have had the backs of their heads immortalized on these videos? Did you call home and ask anybody to identify you? I don't know, but soon each of us has the limelight for 15 minutes a lifetime, right? So, you'll have your 15 minutes.

Here are some nucleic acids.

And let's look at these nucleic acids and the way they are put together.

Keep in mind to anticipate what we are going to say next time, once again, we want to make end-to-end aggregates.

We want to polymerize molecules.

And in this case, we want to do so once again through a dehydration reaction.

And, moreover, just to look at the building blocks of nucleic acids, we start again in this case with two pentoses.

Recall that they have fuor carbons: one, two, three, four, did I say four? You know I meant five.

So, whenever I say four from now on, I mean, or, whenever I say four I may also mean four.

OK, one, two, three, four five.

And let's look at the two basic kinds of pentose molecules that are present in nucleic acid because they define the essential difference between DNA and RNA.

Here's a regular old rather familiar kind of pentose with five carbons.

And here's an unfamiliar kind of pentose which we call deoxyribose. Why? Because if you look really carefully, you'll see that the hydroxyl group here, which should be present in any self-respecting pentose is missing, and is replaced simply by a hydrogen group, i.e., it's lost its oxygen, whence cometh the word, ?deoxyribose,? and ultimately clearly the word, ?deoxyribose nucleic acid.?

And one of the attributes, one of the virtues of carbohydrates, as we discussed last time, were these numerous hydroxyl groups, which represent opportunities for all kinds of dehydration reactions which can enable one to build much more complex molecules.

And here, we see the structure of, for example, a deoxyribonucleotide whose detailed structure we'll get into next time.

But just, let's look at how these hydroxyl groups have been used.

The hydroxyl group, in this case in DNA, and by the way notice that the structure I've shown here, there's a side chain attached here, and a side chain attached here.

And neither of those depends on whether or not there is a hydrogen or a hydroxyl right here.

And look at what's happened here.

Here, we have this hydroxyl over here to which a base has been attached covalently, once again, by a dehydration reaction.

And here, we have a situation where actually three phosphate groups have been attached to the hydroxyl group in this direction.

And, this represents the basic building blocks of nucleic acids.

Now, one of the things that's going to be really important and that you're going to have to memorize, I told you, you weren't going to have to memorize anything.

But you didn't believe me, did you? Good.

OK, one of the things you're going to have to memorize is the numbering system here.

This is number one, two, three, four, five, or to be totally frank, and you know I'm always that, one prime, two prime, three prime, four prime, five prime.

And that numbering system, it turns out, is going to be very important for our subsequent discussions.

Notice here that, for example, it's here at the two prime position that this deoxyribose is lacking the oxygen that is present normally in RNA.

And, with all this in mind, we will wait in great suspense until Wednesday when we actually talk about how this is exploited to make highly complex polymers.



Comments:

  1. Dagal

    I find that you are not right.

  2. Dorn

    In my opinion, this is obvious. I advise you to try google.com



Write a message