4.  Kevin Ahern’s Biochemistry – Protein Structure I

4. Kevin Ahern’s Biochemistry – Protein Structure I

Professor Kevin Ahern:
How’s everybody doing? You’re doing better than I am, huh? Okay, so we are moving our
way through protein structure and one of the things I
wanted to say something about, there’s a couple of things
about amino acids I didn’t finish saying something about, so I’d like to make sure
that you’re aware of them. There’s some terms that I use, and they involve some
calculations as well. One is the term PI. You have probably seen them
on one of the problem sets and I haven’t explained that to you. So I want to say a
little about what that is. So PI is a pH. It’s a special pH. It’s a pH at which a
molecule, that’s any molecule, has a charge of exactly zero. The PI for a molecule must
be calculated precisely. It’s not something that some
of the estimates that I give you will work. Now one of the estimates
that I’ve given in the notes, I haven’t talked about
it specifically in class but I’ll mention it here also, is- there is an estimate you
can make for the charge of a molecule based
on its pH and its pKa. And this estimate that I’m
going to give you for the charge of a molecule only works for estimating. It does not work for calculating PI. So here is the estimate,
this estimate is one I will not give you on an exam. You’ll need to know what I’m
getting ready to tell you. I give you formulas, I
give you various things, but I am not going to give
you what im getting ready to tell you and that is
that to estimate the charge of a molecule, if the pH
is one or more units above the pKa of the molecule
or of a given group, we have a molecule where
there is more than one. If the pH is more than one
unit above the pKa of the group then the proton is off. If the pH is one or more units
below the pka then the proton is on and that’s good for estimating charge and we’ll use that frequently. So you’re going to have to
estimate charges of amino acids, you may estimate charge
of proteins and so forth, that’s very good for that estimate. It’s not good for calculating PI. Now I’m not going to go
through how you calculate PI here because I have a video online that shows you how to calculate PIs. People think that the
only videos in this class are the ones that are under
this column on the left. In fact, if you look on the right you’ll see problem solving
videos here and here and there’s more as you go further down. Practice protein charge problems here. If you watch those videos and
you work through those problems you will have some good practice. How do you calculate the PI? The PI is calculated as the
average of the two pKa values around where the molecule has
a charge of approximately zero. So when you look at a titration
plot you’ll see a place where a molecule has a
charge of approximately zero, it’s the average of the
two pKa values around that. That means that you can’t just
add up the pKas and average them, you got to do a plot
and figure out where that approximate zero
point is and then average the two pKa values on either side of it. If you watch the video
it should help you and if you have questions after
that then of course come see me. PI is a very important
thing because it’s the place where a molecule has a
charge of exactly zero and we’ll see later that there’s
sometimes when its useful first to know when a molecule, a protein, an amino acid or whatever, has a charge of approximately zero. We’ll see when that occurs. Another term I haven’t
used, that I’ve mentioned also I think in my highlights,
but I’ll bring it up here, is the term zwitterion. Z-W-I-T-T-E-R-I-O-N You can bet if I spell it for you
its spelling must be important. Zwitterion is a molecule
who’s charge is zero. So you say well it’s the same
thing as PI, well no PI is the pH at which the molecule
has a charge of zero. A zwitterion is a molecule
whose charge is zero. Two different things. Okay, excuse me, alright. So I wanted to make sure I
got those out there because there are some practice
problems I’ve gotten to work, and who knows, you might
even see something like that on an exam, so its entirely possible that you’ll have that happen. I want to make sure that your
familiar with those things. Questions about that? No questions, okay? Question, Yeah! Question was, ‘do I mean zero
charge or net zero charge.’ And the answer is, same thing. A molecule has a zero charge
if its net zero charge is zero. Alright well, let’s see, so
last time I got to the point of talking about Ramachandran plots, and I don’t want to
make too big of a deal out of Ramachandran
plots because students go, ‘Oh my God, what do I have to know ‘about this, et cetera et cetera.’ Well what you have to know
about Ramachandran plots is first of all,
they’re theoretical plots that tell us something
about the structure that a protein can have. It tells us something
about the structure. Alright, So this was
the Ramachandran plot that I showed you last time and I noted that there
was an awful lot of space on a Ramachandran plot where
structures are not stable now I’ll remind you that
a Ramachandran plot has a plot of phi and psi and there’s three hundred and
sixty degrees for each one, from plus one eighty
to minus one eighty, from minus one eighty
to plus one eighty. These are rotational angles of the two bonds
around the alpha carbon. I don’t care if you
memorize which one is which. That’s not an important thing. But what is important is the
fact that there’s only certain rotations around those
bonds that give rise to stable protein structures. Anything that’s colored up here is relatively stable, the
darker it is, the stabler it is. And the whites are basically regions of rotation around those
bonds that are not stable. Now we’re going to see
in a little bit that some of those rotations correspond
to very specific structures that are commonly found
inside of proteins. Commonly found inside of proteins. Well that’s kind of nice to know. That a theoretical plot
matches up with what proteins actually have and that not only
that but we see commonality, we see these structures
over and over and over inside of proteins
and we’re going to talk something about that. So that’s the sort of jist of a Ramachandran plot. You’re not going to draw
a Ramachandran plot, okay? You’re not going to
interpret a Ramachandran plot but you should know something
about what a Ramamchandran plot tells you. Well, I’ve just finished talking about what I’ve been discussing so
far which is primary structure. I’ll remind you that primary
structure was the sequence of amino acids within a protein and I said that the sequence
of amino acids in a protein determine everything,
ultimately about the protein. We’re going to turn
our attention now from primary structure to
secondary structure. And as we go higher levels of structure we start thinking about interactions between amino acids that
are further and further away. Primary structure was the sequence and the sequence related to the immediately adjacent amino acid. This amino acid, this amino acid, this amino acid in a protein, okay? There’s no distance, the very
next one is the one that matters. Well with secondary
structure we expand that view out to about ten amino acids. So secondary structure,
I’m going to give you a definition here, secondary
structure is a regular, repeating structure that
arises between amino acids, less than ten apart. Less than ten amino acids apart. Is a regular, repeating
structure that arises as a result of interactions between amino acids that are ten or fewer apart. Now that’s a definition. In reality, what does
secondary structure mean? For our purposes we’re
going to talk about two primary types of secondary structure and we’re going to see
that they line up with that Ramachandran plot pretty well. The two primary types
are known as alpha helices and beta strands. And these were the
structures that Linus Pauling discovered and received
the Nobel Prize for. It was his first Nobel Prize. The structure of a protein. Here are four depictions
of an alpha helix. An alpha helix, as its
named suggests is a helix. And you see four different
ways of portraying that helix that protein chemists frequently draw. This one I kind of like, this
is called a ribbon structure it’s sort of like a combination
ribbon and atom structure if it didn’t have those atoms on there we would just call
it a ribbon structure. But ribbon structures are really good for giving us the shape
that a structure would have. If we wanted to be precise
we would actually look at the second structure here,
and this is the depiction of what that short section
of peptide would look like if we looked only at the atoms. It’s a little harder to look at, but it also has an advantage
that in this structure we can see some of the
forces that are stabilizing this alpha helix. The forces that stabilize an
alpha helix are hydrogen bonds. Hydrogen bonds stabilize an alpha helix. You see them in this structure here as little green dashes. These little green dashes
arise between amino acids that are between four to
seven amino acids away. That’s less than ten. Notice that the definition I
gave you said it’s a regular repeating structure. What does that mean? Well, a coil is a regular
repeating structure. That’s what this alpha helix has, that’s what this is trying to portray. What else can we say
about an alpha helix? Well, what we can say also
shows up nicely in both C and D. If we look at those green
dots that are on there, on each of these, the greens correspond to the r groups. Now if we look at this, we see in an Alpha helical structure, that the r groups are pointed
outwards from the helix, that’s nice. Some of you have asked me individually and I think somebody
asked in class also, do some amino acid side chains effect the structure of the protein? The answer is yes they do. We try to put two bulky side
chains next to each other that it may very well disrupt and prevent an alpha helix from forming. Now we can actually
use computer programs to analyze an amino acid sequence and predict with a
reasonable amount of certainty if a given segment of a protein
is present in an alpha helix. A computer program can do
that using the knowledge that we have of the
r groups and so forth. So, that’s something that a
computer can do for us quite readily. This shows some of the
interactions between hydrogens and oxygens,
and oxygens and hydrogens within an alpha helix. And we twist these around
in three dimensional space, something that looks like its
far away in primary sequence actually ends up being pretty close to each other in secondary structure. So this and this are fairly
close when the alpha helix forms. If we look at the
Ramachandran plot, we see Ahh! There are two places
on the Ramachandran plot where the helices can form. One is a right-handed
helix, which is very common, And the other is a left-handed
helix which is very rare. But, they appear right
square in the middle of predicted regions of
stability by Ramachandran. This is a nice depiction of a protein that’s full of alpha helices. Now you’ll notice that this alpha
helix doesn’t just go forever, it’ll have a little bend sometimes, sometimes it will have a bigger bend and we’ll talk about those
bends when we talk about tertiary structures. But suffice it to say that there
are proteins that have almost exclusively alpha helical structure. Not all proteins, but
some proteins have that. Alright, another common
secondary structure, and the second one
described by Linus Pauling, are known as what some
people call beta sheets. I like to call them beta strands. If we take beta strands and we arrange them
together we get a sheet. So a sheet is an arrangement
of a bunch of beta strands. We’ll start here with the
Ramachandran, and look, oh wow! The beta strand’s structure
right square in the middle of the theoretical region of
stability in the Ramachandran plot. What is a beta strand? Well, let’s talk about that. Here’s what a beta strand looks like. It’s a little hard to tell from
this figure what it looks like. But a beta strand is like
a helix in two dimensions. A helix goes round,
and round, and round, a beta strand is like
and also called pleats. Up, down, up, down, up, down,
up, down, up, down, like that. So it’s a flattened, two-dimensional
version of an alpha helix. Alright, this depicts that up,
down, up, down, pretty well. Okay, up, down, up, down, up,
down, up, down, up, down, okay. You see that the greens
again are the r groups and you remember from the structures that we saw before the r groups that they were on opposite
sides every other one, so here’s one in the
back, front, back, front, and here’s the central part
with the carbonyl group, the alpha carbon, and
the carboxyl group, up, down, up, down, up,
down, up, down, up, down, you can see like that. Now, what this shows is interactions between two different beta strands. Two different beta
strands interact like this, they’re going to give
rise to a beta sheet, which is a set of them. Now when we look at this we see that what stabilizes the beta
sheet are hydrogen bonds again. Hydrogen bonds are holding
together beta sheets. We might have a whole stack of
these, we might have ten of them. If we had ten of them stacked
up like that or maybe even more, we would have something known as silk. Silk is full of beta sheets. Parallel versus
anti-parallel simply refers to whether the carboxyl and
the amine are like this, or if the carboxyl and the
amine ends are like this. These are parallel,
these are anti-parallel. If this is the carboxyl
end, this is the amino end, this is the carboxyl end,
this is the amino end, anti-parallel, parallel. That’s all it is. The overall structure
doesn’t matter for parallel or anti-parallel. Here is an enzyme that has a structure that has beta sheets arranged rather nicely into
what we call a barrel. You can see that this barrel and
the blue parts are the strands that are all oriented
with respect to each other. They create a barrel, and
this barrel on the inside is fairly protected from water. Barrels like this we occasionally see when enzymes need to
have water or protection from water for something, or they need to have a reaction
contained within a certain space and barrels work very
well for those things. Now I showed you the
alpha helix and I said, “Alpha helix will go for a
ways and then we see a bend “or we see something else
that sort of interrupts that.” So I want to say a
little bit about things that interrupt structures, specifically things that
interrupt secondary structures. Now I’ve told you that
there are some amino acids that really can cause some changes. One was as I said, things
that have very bulky r groups. If you put two of them together,
they may not fit very well and that may cause a bend if we had an alpha helix going
on for example, or a beta strand. Other things that I’ve said
can disrupt protein structure is proline. Because proline, you may
remember, was the amino acid that had the r group that
came back around and attached to the alpha amino group and
I said it was less flexible. Well what you see on
the screen is something that arises very commonly
as a result of the appearance of proline with in a
polypeptide sequence. “I” here refers to one amino
acid, “i+1” is the next amino acid, “i+2” is the next, “i +3”
is the next amino acid. So here’s a series of four amino acids and what you see on the screen
is a depiction of a bend. Instead of going off in a helical
nature or on a pleated nature, this bend is happening right here. And the bend is happening
because something is not consistent with
that regular structure that we saw for an alpha helix or something that we
saw for a beta strand. As I said, most
commonly bends will arise in a structure like
this because of proline. Proline is not flexible, and also commonly we will see in
a structure like this, glycine. Glycine, you may remember, was the amino acid that
had the smallest r group. and its glycine that allows
for the most flexibility, the most options that are there and glycine may often times
also be in a structure like this. Now bends are important
for us to consider when we start considering the
next level of protein structure and that’s tertiary structure. So I’m leading up to getting
into tertiary structure. I’m not going to talk about
tertiary structure at the moment, I’m going to save that
for a few minutes from now, but suffice it to say
that tertiary structure really has a lot of bends in it. Yah question. Student: [inaudible] Professor Kevin Ahern:
Yeah, what depicts it or what amino acids would favor it? So it’s a good question. So what will tend to favor an alpha helix versus
a beta helix strand? I think I have a link
on here I will show you that some one’s compiled a list
of all the different amino acids and their tendency to be in a
structure that’s alpha helical or a beta strand. There is no absolute rule first of all. There’s no rule that says
tryptophan can’t be in an alpha helix because tryptophan can
be in an alpha helix. Its likelihood may be low depending upon the amino
acids surrounding it, and we start thinking about
amino acids surrounding it, that is what makes our
predictive abilities a little bit harder to do. So I can say for example,
tryptophan is not in an alpha helix, you would say, ‘Okay well
I’ll mark that one off.’ But it can be. So but I’ll show you a table that shows a preference
for one versus the other and then you’ll get a
bit of an idea of it. Is that okay? Yah another question. Student: [inaudible] Professor Kevin Ahern: Do you ever see a hydrogen bonding occurring
with something in the amino group. Let me think about
that one for a second. You will not get with in the backbone because in the backbone the only things that can hydrogen bond there are those that are linked to the amin because you have to have
a partial positive charge and there is nothing in the backbone that would have a
partial positive charge, except for that. If we think about r groups, yes we can have that because
r groups can have a variety of things inside of them but
not inside the backbone, okay? Good question. Alright, now I didn’t want to
talk about tertiary structure yet because I wanted to talk about
a special class of proteins that are interesting
because they only have primary and secondary structure. Most proteins have at least
primary, secondary and tertiary, some will have quaternary,
some wont, we’ll see. Most proteins have at least
primary, secondary, tertiary. But there is a group that has
almost exclusively primary, secondary and very very
little if any tertiary. This group of proteins that has
only primary secondary structure known as fibrous proteins. And as their name would
suggest, they’re fibers. So we can imagine something
that has an alpha helix that just keeps going
and going and going and going and going and going and your hair would be
a really good example. So your hair is full of alpha helices that just go on and on
and on and on and on. Now in individual hair is
comprised of, of course, many individual alpha helices
all meshed up and intertwined, and so on and so forth, so
it’s a little complicated but the important point
is that they don’t fold, they don’t have much in the
way of tertiary structure. If you have curly hair, you
may have some slight bends that happen as a result of some
disulfide bonds that happened that caused some
bending to happen within that overall bigger structure. So people who go, and
people used to go do this and get permanents and things
like that to get their hair styled and curled and so on and so forth would come out of the
hairdresser smelling like stinky because the hair dresser had
to break those disulfide bonds, those are sulfur bonds, they had to use sulfur
compounds to do that and that’s why your hair
stinks after a permanent. Those bonds aren’t permanent though, as you discover if
you have one of those, so they will come apart and they will go back
to its original shape. So even if you get your hair curled, it doesn’t stay curled forever. If you have curly hair, your hair has already
assumed those structures in its most native form, and it’s hard to change that, but again, that’s what a permanent does. Let’s look at some
of these arrangements. So these are coils of coils. Here’s an alpha helix, and here’s an alpha helix
coiled with another one. We can imagine that hair
might have many of these guys, many of these bundles that come together to ultimately make a
hair that we can see. I’ll talk about that another time. Let’s talk about
– don’t do that to me. One of the most interesting
of the fibrous proteins is the most abundant
protein in your body. One of the most interesting
of the fibrous proteins is the most abundant
protein in your body. And the most abundant protein in
your body is known as collagen. Collagen is a very odd fibrous protein, I’ll tell you why in a second. But it is a fibrous protein, it has very little tertiary structure. And it too is a coil of coils. It’s three coils coiled together. So that was actually, here it is. That’s one depiction of it. We see three coils coiled together. We see one strand in
blue, one strand in red, and one strand in yellow. Collagen in the glue
that holds us together. It attaches cells to each other,
it attaches, bones to muscle, and a variety of things. So collagen is really
an important glue for us and that’s why we have so much of it. It’s very very important
for us to have that glue that holds us together. I’m going to tell you
something that’s kind of cool and has medical
implications about collagen. Collagen as you saw, was
in fact, a coiled structure and we can imagine that we
have one coiled structure now that bundles with
another coiled structure and we get sort of super order
of these coiled structures. It turns out that there is a reaction that occurs to modify some of
the amino acids in collagen. We haven’t talked about
modifying amino acids, it’s appropriate now
that we talk about that. Some amino acids in
proteins get modified after they’re put into a protein. They’re modified after
they get put into a protein. In collagen, the two most
common are lysine and proline. After they are made into
the collagen structure, they are modified by putting
a hydroxyl group onto them. Modified by putting a
hydroxyl group onto them. That reaction requires vitamin C. One of the reasons you have
to have vitamin C in your body is so that you can make collagen that has those modified prolines
and lysine residues there. I’m going to tell you why
they are important in a second, but you need to understand
what they are first. Now you’re probably sitting
there scratching your head going, ‘But Kevin, you said that proline disrupted-‘ I’ll tell you what it’s disrupting
right here is the collagen… If proline is so disruptive, what’s it doing inside
of this helical structure? Well it turns out it’s everywhere
in this helical structure. And what’s interesting about
it is wherever we see a proline, we almost always see a glycine. Pro, Gly, Pro. This is a little bit of a
clue as to what’s going on. Proline being very inflexible,
glycine being very flexible, put the two together, helical
structure become possible, very very possible. So this is one of the reasons
it’s an odd fibrous protein. Now proline, as I said, gets modified. It gets hydroxide groups
put onto it as does lysine and it turns out that
those hydroxide groups are reactive towards each other. Hydroxyl of a proline
on this strand over here or this bundle over here may
react with a hydroxyl on a proline on this bundle over here
and when they do that, they split out water
and make a covalent bond. Covalent bonds, as we
remember, are very very strong. Why is that important? I’ll tell you why it’s important. I see several people
on here with long hair. If you braid your hair or
you’ve braided somebody’s hair, you know that you can take it and you can make beautiful
braids with the hair, but if you don’t tie it off at
the bottom with a rubber band, what happens? It will all come out. The equivalent of the rubber
band are these covalent bonds that form in between
these hydroxyl groups in the individual bundles or strands that I am describing for collagen. What these bonds give to
collagen is great strength and when we talk about holding
our bodies together as a glue, we want great strength. We don’t want to fall apart. Now I tell you that because, vitamin C, I told you, was necessary to
make those hydroxyl groups. If we don’t have vitamin C, if
we are deficient in vitamin C we develop a condition known as scurvy and scurvy is not something
you want to experience because what happens is
you literally fall apart. Your collagen is very weak. The rubber band at the end of your hair, or at the end of our collagen
isn’t holding stuff together, you’re in bad shape. Scurvy was discovered
first among the pirates who went off on long voyages
with no fruits and vegetables etcetera etcetera, those silly pirates. And they went out as big,
honking, ugly, mean, old pirates and they came back a bunch of wimps. They fell apart. Vitamin C is important
for that reaction. It’s important for
making a strong collagen. Questions about that? Yes? So vitamin C strengthens collagens because vitamin C is necessary
for adding the hydroxyl groups to the lysine and proline residues and those lysine hydroxyl
groups react between the individual strands
to help hold them together and make them stronger. Just like if we made a
braid, like for a rope, the braid is going to be stronger
than the individual strands will be by themselves, make sense? I’m sorry? It’s not a catalyst, no.
It’s a necessary sub straight for the reaction. Okay good questions. So that’s what I want to say
about secondary structure. Let’s turn our attention
to tertiary structure. Now as I said earlier, the
higher the level of structure, the further apart the interactions are. This is a structure of a protein that we are going to talk a
fair amount about next week, it’s called myoglobin. Myoglobin is a protein
that is not fibrous. If a protein is not fibrous,
we refer to it as globular. Most proteins in nature are globular. Fibrous proteins are not very
common in terms of number, they are common in terms of abundance, like we have a lot of collagen, but collagen is only one protein. Most proteins are globular. What does it mean to say
something is globular? Well I like to just be silly and say if we were to actually
look at this protein sitting on the stage right
here it would look like a glob. It would not look very
regular in structure. It would’t have nice pretty coils going forever and ever and ever, but it would have little
coils that would go for a ways, and then we would get a bend,
and now you know how bends happen. Mercedes-Bendz, ha ha. Bad joke. You guys want a joke? You ready for a joke? I tell this one in
my class all the time, I love this joke, it’s my
favorite joke in the world. If you’ve ever watched my videos
you probably have heard this joke so don’t give away my punch line. This is about the hit man known as Arty. How many people have
ever heard the joke? A couple, okay not too many. So there’s this little guy, he’s
a hit man, and his name is Arty. He decides he wants to make
it big in the hit man business. If you want to be big
in anything these days, what you have to do is
you have to advertise. So he take a little business
card and he puts on there, “Will kill somebody for cheap,” and he posts it all
over his neighborhood. So he’s sitting at home one
night and he gets this phone call, and somebody’s gotten his business
card and they call up and say, “Hello are you Arty?” And he says, “Yes, yes.” And he said, “Well I’ve got
somebody I’d like you to kill.” He says, “Okay.” And he says, “But how
much do you charge?” He said, “Well I’m just getting
started, I’ll do it for a buck.” This guy says, “Okay, yah yah.” So Arty says, “Who do
you want me to kill?” And he says, “Well, I
want you to kill my wife.” It’s always the wife, right? It could be the wife wants to
kill the husband, doesn’t matter. I want you to kill my spouse. “Alright well I can do that, “is there any way you’d like
me to kill them or anything?” He says “Yah, I’d like
you to strangle them.” He said, “Okay,” and
he writes this all down. “And where can I find them?” “Well my spouse is down at
the grocery store right now, “could you go down and do that?” Arty says, “Sure, why not?” Arty goes trucking down to
the grocery store and he looks, and he sees in the grocery store, he sees this person that
meets the description. “Ahh, my career is starting right here, “right here in the produce section.” So he goes up and he grabs the
spouse and he starts strangling and kills the spouse right
there in the grocery store. Yes, he’s done it, right? Oh no, somebody saw him. Somebody saw him so
he’s got to do something. So he goes over, what
else is left to do? You can’t have any witnesses. So he goes over and he grabs
this person and he strangles them! That was close. Oh no, over here, right? “My lucky day, right? “I’m starting my career as a
hit man and I get a witness.” So he goes over and he
grabs this other person and strangles them right there, and he looks around and there’s nobody. “Yes!” So he goes running out the
door, but the police catch him. And the headline in the
newspaper the next day says, “Arty Chokes Three for a
Dollar at the Grocery Store.” [laughing and clapping] Thank you! [laughing] You see why that’s my favorite joke. “Arty Chokes Three for a Dollar…” It takes a while to set that
one up, but it’s a good joke. Don’t tell your friends, that way when they take
this class next year, they won’t have heard
the joke, that’ll be good. Okay, back to tertiary structure. So tertiary structure arises
because of Mercedes-Bendz. The joke still doesn’t work
I guess, after that joke. But what we have are alpha
helices that go for a ways and then they turn, they go
for a ways and then they turn, they go for a ways and then they turn. Those turns give rise to a
three dimensional structure. When we think about the three
dimensional structure of a protein, the turns are really critical because slight changes in those turns point the helix in a very
different kind of direction. What matters is the overall
three dimensional nature, the tree dimensional
structure of that protein, and this protein when it’s in
its proper three dimensional form carries oxygen. That little thing right here
is known as a “Heme group” that we’ll talk about
later that caries oxygen. So globular proteins have a
three dimensionality to them, they have more than just
a fibrous nature to them, and they also have some
bias when we talk about what amino acids that
they have with in them. Notice here blue is charged, yellow is hydrophobic,
and white is other. Blue charged, yellow
hydrophobic, and white other. Blue charged, yellow
hydyrophobic, white other. What you see on the screen for
this particular globular protein is that there’s a
bias in the amino acids in this overall structure. Polar or charged things tend to
be on the outside of the protein. Non-polar, uncharged things
tend to be on the inside of the protein. That makes really good sense. Most proteins are dissolved
in water in the cell, and for them to dissolver in water, you want to have the
polar and charged groups interacting with water, and the things that don’t like
water will fold unto themselves and avoid the water. There’s no water on the
inside of this protein because these hydrophobic
groups have squeezed it out. They’ve squeezed it out. Not all proteins are dissolved in water, we’ll see some exceptions later, and when we see those exceptions we’ll see that they’re reflected also in the location of
amino acids with in them. In fact, I said later,
here’s one right here. Here’s one called “porin.” Porin is a protein that is
found in membranes of cells. Membranes of cells are fairly non polar. So we see the outside of this guy, the part that’s interacting
with the membrane, it’s fairly non polar. On the inside, porin, what it does, is it allows water to pass through it. It’s a pore. And we see on the inside of this
guy, here are the hydrophilics, or the polar charged groups,
that allow water to interact and come in through there. These last two figures I’ve shown you are probably the best
examples I can give you of structure and function. Now, I did bring up a song, so I think we’ll
finish today with a song and then we will talk
more about his next time. Another easy song to sing. It’s called, “Oh Little
Protein Molecule.” Professor Kevin Ahern and
Students: Oh little protein molecule you’re lovely and serene. With twenty zwitterions like cysteine and alanine. Your secondary structure has pitches and repeats, arranged in alpha helices and beta pleated sheets. The Ramachadran plots are predictions made to try to tell the structures you can have for angles phi and psi. And tertiary structure gives polypeptides zing because of magic that occurs in protein folding. A folded enzyme’s active and starts to catalyze when activators bind into its allosteric sites. Some other mechanisms control the enzyme rates, by regulating synthesis and placement of phosphates. And all the regulation that’s found inside of cells reminds the students learning it of pathways straight from hell. So here’s how to remember the phosphate strategies. They turn the GPb’s to a’s and GSa’s to b’s. Professor Kevin Ahern: Well
talk more about those later.