I have described so far how enzymes
are flexible around the active site
and how that flexibility at the active site
facilitates the catalytic process that happens.
But enzymes are flexible all over.
And that flexibility all around the enzyme gives the enzyme
some interesting properties as regards its activity.
Now we can see here on the left an enzyme that is getting
ready to bind a substrate, as we have seen before.
And on the right we see the enzyme after having
bound to substrate has adapted itself
to the shape of the enzyme. This was the
induced fit that I have been referring to.
This induced fit makes a lot of sense
for the active site, as I said.
But the rest of the enzyme is also
affected by these interactions.
Now this has actually manifested itself in the
plot that is shown on this figure right here.
On this plot we can see the V versus S
binding for an enzyme that's allosteric.
Now I remind you that allosteric
means that the enzyme is interacting
with a small molecule and having its activity affected.
In this case, the small molecule that's interacting
with its affecting it, is actually its substrate.
So this happens with multisubunit enzymes.
Now what I am getting right to describe
very much parallels what I talked about
with hemoglobin's binding of oxygen
in another of the presentations.
When hemoglobin binds to oxygen, you may recall
that the binding changed as the
oxygen concentration increased.
As the oxygen concentration increased, hemoglobin's
affinity for oxygen went from low
to high and that was important
for the action of hemoglobin.
The same thing can happen with an enzyme
whose affinity can change depending
in terms of binding of the substrate
that affects it allosterically.
Now multisubunit enzymes have this happen; because,
one part of the enzymes binds its substrate
and affects the binding of the
substrate on other parts of the enzyme.
Now this change that I have described to
you results in a change in the
overall physical shape of the
enzyme, not just the catalytic site.
Now this overall change of the enzyme
is given a couple of names. First
we talk about a state that's relaxed.
It's called the R-state. The
relaxed state of an enzyme
is the state that really the enzyme is open to binding
substrate and is very able to bind substrate.
The relaxed state of an enzyme corresponds
to a more active state of the enzyme.
By contrast the T-state of
an enzyme, where T stands for tight,
is the enzyme is tensed; it
is tight; it is not flexible,
and it is not able to
bind substrate as well.
On this plot for example, we can see at the low substrate
concentrations the enzyme is in the T-state.
It's not binding substrate very well. But once the
substrate concentration gets high enough
the enzyme flips.
And then it is able to bind substrate better.
So its velocity change actually flips. We don't
see the hyperbolic plot that we saw before.
Well there is a couple of ways people have studied
and tried to explain this phenomenon going on.
So I wanna spend a little time
going through and explaining
ways that we interpret this change.
They are called the concerted model
and the sequential model.
So the first of these, I will talk
about here, is the concerted model.
The concerted model is conceptually a
little hard to get one's head around.
We see the enzyme in this model, existing in
two states, and for the purpose of this
illustration we assume that
this enzyme has 4 subunits.
Enzymes can have many many subunits
up to at least a dozen subunits in some
cases. But for this illustration it has 4.
In the T-state we have the enzyme shown in the
squares on the top and the T-state where we call is
the least favored of the states.
The circles below refer to the enzyme in
the R-state where the enzyme is relaxed
and more able and more likely to bind substrate.
What the concerted model says is that the flipping
between the T-state and the R-state
happens completely as shown.
There is we go from top to the bottom,
and there is no intermediate.
And what this model says is something
that seems counter-intuitive;
because, this model says that
the flipping from T to R
is not caused by the binding of the substrate.
But rather the R-state or the T-state is favored
by whatever the state it happens
to be it will not bind substrate.
So if I have an enzyme that flips into
the R-state and it binds substrate,
the substrate will lock it in the R-state.
So that it will tend to stay in the
R-state and consequently be more reactive.
If the enzyme binds it in the T-state,
it's like to stay in the T-state.
Once the enzyme is in the R-state it's gonna stay there
and keep producing and since the R-state is producing more
and more of the product,
anything that favors or locks in the R-state
is going to favor the reaction more.
So the concerted model is
an all or none. But the locking into one
state or another is central to what it does.
You can see here that there is equilibrium between the
two, and the equilibrium shifts as we get more
of the substrate binding or
locking it into a given state.
As we go further to the right,
the R-state is favored; because,
there is more enzymes now in that R-state,
and more enzymes means more product.
The R-state can flip, as I said,
independently of each other
but the bound state is favoring
in this case the R-state.
Now the other model that we called the sequential model
is very much like what we saw when I described
the flipping or the changing of hemoglobin.
We also refer the states, R-state
and T-state, in hemoglobin
but we more commonly used
this as regards enzymes.
Now in this model what happen is we have
an enzyme that starts out in the T-state
is shown in the 4 squares on the left.
The binding of the first substrate causes one
of the subunits of the enzyme to flip.
And that's shown in blue in
the second model from the left.
When that flipping occurs, the blue interacts
with the other two units of the
enzyme and we can see that there is sort of a
purple that happens and a rounding of those two.
That's indicating that the blue
circle which is in the R-state,
is affecting the two units around it
and causing them to start
to flip into the R-state.
Well the starting to flip favors the binding in more
substrate and so we can see sequentially then
that the blues are becoming more dominant
as we get further to the right.
The binding of the substrate
is a critical thing for
this enzyme; because, the binding of the substrate
in this model says it's the cause of the flip.
Now casually when we talk about it, we frequently say
"Well this causes the enzyme to do this or that",
and when we say that, we sort
of loosen the language that we use.
In this case the cause is physically
causing the flipping to occur.
In the concerted model the cause is not a direct
but it's an indirect as a result
of the locking that I described.
So the distinguishing difference between the
concerted model and the sequential model
is that cause that I mentioned.
Causing the flipping is a physical causing.
The two models that I have just described, the
concerted model and the sequential model
are just that. They are just models in terms of explaining
how the T-state and the R-state come to be within enzymes.
It's very likely that no enzyme actually uses
exclusively one of the other and
there is a lot of evidence that
enzymes may use a sort of a hybrid of these two models.