Allosteric Enzyme Conformations

in this video, we're going to begin our lesson on Alice Terek enzyme confirmations, so recall that protein confirmations are really just alternative three dimensional states or forms that a protein can achieve. And so recall from our previous lesson videos were recovered protein structure that proteins are not completely rigid structures, and instead we know that protein structures can be induced to changes. And again, we know that from our previous lesson videos, where we covered the induced fit model that enzymes and proteins can display. And so it's important to note that different confirmations that proteins can take on can actually have different abilities and or functions. And so, in our next lesson video, we're going to introduce the two confirmations that Alice Derek Enzymes can take on. And those two confirmations are going to have different abilities and or functions. And so we'll be able to talk more about that in our next lesson video. So I'll see you guys there

So from our last lesson video, we know that Alice Derek enzymes have to protein confirmations or states. And those two protein confirmations are the T state and the our state. And so Alice Derek enzymes can exist in either one of these two states. And so again, the two states are the T state, which stands for the tense state and the our state, which stands for the relaxed state. And so the Alice Terek Enzyme Confirmation T state is a catalytic lee inactive state. And so because it is catalytic Lee inactive, that means that it's going to have a low affinity for the substrate. And so, when the Alice Terek enzyme is in the T state confirmation, the Alice Derek Enzyme is going to bind substrates very inefficiently. So the other Alice Terek enzyme confirmation is the our state and the our state is essentially the opposite of the T state. And so the our state is a catalytic lee active state. And of course, this means that the our state is going to have a high affinity for the substrate. And so when the Alice Derek Enzyme is in the our state confirmation, the Alice Derek enzyme is going to bind substrates very, very efficiently. And so notice down below. In our example on the left hand side, over here, what we have is an Alice Terek enzyme that has two different sub units, one sub unit right here and a second sub unit right here. And so notice that this is actually the T state confirmation of the palest Eric enzyme. And of course, the T State is the tense state. And so notice that the active sites here that are supposed to be binding substrate represented by this blue circle the active sites are in a tense confirmation that are very, very small. And therefore, the Alice Derek enzyme in the T state is not going to be able to bind substrate very, very efficiently. And so that means that the Alice Derek Enzyme is going to be inactive and bind with low affinity to the substrates. And so that's why we have these axes here to show that the substrate cannot bind very efficiently to the T state. Now, over here on the right hand side, what we have is the same exact Alice Terek enzyme. Just in a different confirmation this time it's in the our state confirmation in the our state is the relaxed state. And so notice that the enzymes active site is in, um, or relaxed confirmation. It's much more open. And for that reason, the our state is the catalytic lee active state that binds substrates very, very efficiently, and so notice that the substrate can easily bind into the enzymes active site. When the, uh, enzyme is in the our state. And so notice down below. We have these images to help you guys better understand the T state and the our state and again recall that the T State is really the tense state. And so when you think about the 10th State, you can think about Arthur's tense fist right here. And so Arthur's fist is so tight there's no way he's going to be able to grab onto anything. And so there's no way that a substrate is going to be able to fit in here because it's simply so tense. And so you can also think of the T state of the Alice Derek Enzyme as a balled up piece of paper, which is also very, very tensely balled up. And when it's so tense again, it's pretty hard to get a substrate to get to the inside and bind to this balled up tense state. Now notice. Over here, what we have is the relaxed state and so notice that Arthur's fist has actually become much, much more relaxed. And it looks like Arthur even got himself a nice looking manicure. And so, when the, uh enzyme is in this relaxed our state, it's much, much easier for a substrate to fit into the enzymes active site. And so the our state bind substrates very, very efficiently and also noticed what we have is in, ah, piece of paper that is a little bit uncritical ditz, not as balled up intense as it was over here. So again, it's much easier for a substrate to make its way into and bind to the active site. And so, hopefully all of these memory tools here will help you guys distinguish uh, the Tea state from the our state, and we'll be able to get some more practice utilizing all of these concepts as we move along through our course. So this concludes our introduction to the T state in our state, and I'll see you guys in our next video

in this video, we're going to introduce the Alistair Constant l not. And so the ballast Eric Constant is represented with the variable l not. And really, all the Alice Derek Constant is is just a ratio. It's the ratio of the concentration of t states over the concentration of free our states essentially the ratio of the concentration of tea over the concentration of our but specifically when there is no substrate, that's present. And the reason for that is because it turns out that this ratio of the T states over the our states can actually change when we change the concentration of substrate. But we'll talk more about that idea later in our course. For now, all I want you guys to know is that the Alice Derek Constant l not is just this ratio of tea over our when there is no substrate present. And so, under these conditions, when there's no substrate essentially at very low substrate concentrations, it turns out that the t state is actually mawr favorable Thermo dynamically favorable. Then the free our state, which means that at these low substrate concentrations, when there's no substrate present the equilibrium between the T state and the our state is going toe favor the T state. And so if we take a look at our image down below to try to clear some of this up notice on the left hand side, what we have is the same Alice Derek enzyme from our previous lesson videos. And we know that it's in the T State over here, since the active site does not bind substrate efficiently. And then over here, what we have is the our state of the Alice Terek enzyme. But notice specifically that this is actually the free our state of the palest Eric enzyme, which means that it has not yet bound any substrate. Notice that the active sites are in a relaxed state, but they're not yet binding toe any substrate. As soon as the substrate comes and binds to these active sites, it becomes a substrate bound our state. And so you can see here that these substrates are now bound to these active sites. And so again, these substrate bound our state down here is different than the free our state. And so this is important because the Alice Terek Constant, which we know is abbreviated as l not Is the ratio of the concentration of t states over the concentration of free our states, not the concentration of substrate bound our state. So specifically l not is telling us about this particular equilibrium, and it does not involve the substrate bound our state. Now, over here on the right hand side, notice what we're showing you at the top is that at low substrate concentrations, essentially, when there's no substrate, that's present. As we already know, the equilibrium between this t state and the free our state is going to favor the Tea State. And of course, if the equilibrium favors the T State under these conditions, then what that means is that there's going to be a lot more t state, then free our state. And that means that this ratio right here indicated by L, not the Alistair Constant is going to be quite large, if again, there's a lot of t state and not a lot of our state. And so here What we can say is that we're going to have a very, very large l not under these low substrate concentrations again when there's no substrate present and so notice down below right here. What we're showing you is the enzyme in the T state is represented by these pink boxes and the enzyme in the free. Our state is represented by this green circles. And so notice that at low substrate concentrations essentially where there's no substrate notice, there's no substrate represented here in this image that there's ah lot Mawr t states than there are free our states. And so this goes to show that the equilibrium does indeed favor the T states under these low substrate concentrations, where Elna is going to be large, so down below, right here. What we have is a little memory tool for the Alistair constant l not to help you guys remember that it's the ratio of the concentration of t states over the concentration of free our states and not vice versa. And so when you consider the Alistair a constant al, not we know it's gonna be equal to some ratio. We know that we write ratios with lines just like this, and this line can remind you of a tight rope. And so hopefully that will help you guys remember. Lauren is tight roping over a relaxed crowd and so notice. Here we have Lauren and noticed that Lauren as tight roping here over a relaxed crowd and so that can hopefully help you guys remember that the Alice Derek Constant l not is just the ratio of the T states over the concentration of our states and not vice versa. And so moving forward, hopefully utilizing this memory to will help you guys out a little bit. And this concludes our introduction to the ballast Eric Constant Elna and how it relates to the Alice Terek enzyme confirmations. And so moving forward in our course will be ableto learn even mawr about Alice Terek Enzyme confirmation. So I'll see you guys in our next video.

in this video, we're going to talk about how Alice Terek enzyme confirmations essentially the T in the our state confirmations allows for cooperative kinetics. And so recall from our previous lesson videos that Alice Derek Enzymes display sigmoid all kinetics, which means that on an enzyme kinetics plot, they display an s shaped curve just like the enzyme kinetics plot down below showing the S shaped curve right here in blue. And so what we haven't yet mentioned is that the sigmoid it'll kinetics that's displayed by Alice Derek Enzymes actually suggests that substrate binding to the Alice Derek Enzyme is a cooperative process. Now it turns out that there's actually multiple types of cooperative ity. There's negative cooperative ity and positive cooperative ity. Now, later, in our course, we'll talk about negative cooperative ity. But it turns out that the sigmoid all kinetics displayed by Alice Derek Enzymes actually suggests positive cooperative ity and so positive cooperative ity. It's just this idea that binding of one substrate molecule to the Alice Derek enzyme actually ends up making it a lot easier for other substrate molecules to bind to the Alice Terek enzyme. But how exactly does cooperative substrate binding work. How is it that the binding of one substrate molecule could make it a lot easier for other substrate molecules to bind? Well, in order to understand that, we need to recall from our previous lesson videos that when there is no substrate concentration essentially at very, very low substrate concentrations the equilibrium between the t state which notice? Over here we have the T state of our Alistair Genzyme. So this equilibrium between the T state and the free our state over here. So this equilibrium at very, very low substrate concentrations favors the T state, as we already discussed in our previous lesson videos. However, it's important to note that increasing the substrate concentration from low substrate concentrations toe higher substrate concentrations will actually disrupt this equilibrium between the T state and the free our state Essentially this equilibrium right here and so ultimately what we'll see is that substrate binding to the free our state will produce substrate bound our state. So notice here we have the free our state that does not have any substrate bound bound to it on dso When we start to increase the substrate concentration, the substrate is more likely to bind to the free our state. And when it binds to the free our state it forms the substrate bound our state down below. Now, of course, substrate binding to the free. Our state does produce the substrate bound our state. But it also consequently decreases the concentration of free our state. And so if the concentration of free our state is being decreased, going down to form substrate bound our state, then that means that this equilibrium right here is going to shift to the right to compensate for this decrease on that is explained by less shot liaise principle. And so again, lowering the concentration of free. Our state right here is going to cause the reaction to shift to the right here towards production of the free our state. And so you can see that the binding of a substrate molecule to the free our state is going to decrease the concentration of our state and cause other proteins and the T state to shift into the our state. So essentially, the binding of a substrate molecule makes it easier for these enzymes to shift into the our state and bind substrate molecules as well. And That is exactly what explains positive cooperative ity. Binding of one substrate molecule makes it easier for other substrate molecules to bind to the enzymes. And so notice over here in this enzyme kinetics plot on the right again, we have the sigmoid all kinetics of our Alice Terek enzyme and notice that the E s concentration here the enzyme substrate complex concentration eyes, actually representative of the substrate bound our state right here. And so notice that when we have very, very low substrate concentrations, the concentration of the substrate bound our state is really, really low and much, much less than the total enzyme concentration represented by the concentration of E. T here. Now, as we start to increase the substrate concentration towards the right notice that the initial reaction velocity begins to increase, the initial reaction velocity here begins to increase. And at this point right here noticed that the concentration of enzyme substrate complex, which is again, uh, the concentration of substrate bound our state is actually increasing. And now, at this point, it's equal to half of the total enzyme concentration. Instead of being much, much less than the total enzyme concentration and then of course that we continue to increase the substrate concentration even further to the right. Uh, then the initial reaction velocity starts to approach the maximum reaction velocity V max and at saturating substrate concentrations the concentration of enzyme substrate complex, which is again the substrate bound. Our state is going to equal the total enzyme concentration, which means that all of the enzyme will be bound to substrate in this form. And again, that's going to allow the reaction to proceed at its ah, near its maximum velocity v max. And so this here is our introduction toe. How Alice Terek enzyme confirmations tion are confirmations allow for cooperative kinetics. But later, in our course again, we're going to talk mawr even more details about cooperative kinetics, specifically negative and positive cooperative ity. And again, this is just our introduction. So as we move forward in our course, we're going to continue to learn Mawr and Mawr about our Alistair enzyme. So I'll see you guys in our next video

in this video, we're going to talk about how the Alice Terek Constant l not really dictates the extent of an al hysteric enzyme. Sigmoid I'll curve. And so the greater the value of the Alistair Constant Elna, the more sigmoid all the curve will be on an enzyme kinetics plot of the initial reaction velocity versus the substrate concentration. And so, of course, what this means is that the smaller the value of the Alice Derek Constant l not the Lessig Moyal the curve will be. And the mawr, the curve will resemble meticulous meant in kinetics. And so if we take a look at our enzyme kinetics plot down below, notice that we've got these three different curves. We've got this green curve right here. We've got the pink curve right here and we've got the black curve over here. And so notice that were also given the Alistair constant for each of these three curves and notice that as the Alistair constant increases, the more sigmoid all the curve becomes. And so because the green curve here has the largest Alice Derek Constant, it is the most sigmoid All, of course, the pink curve has an intermediate Alice Derek Constant between the three curves and that makes it have a slightly less sigmoid curve. And then the lowest Alice Derek Constant here, eyes going to be the one that is least sigmoid oil and most resembles, the McHale is meant and kinetics showing a rectangular hyperbole. And so if the Alistair Constant goes even lower than one, then that just means that it's just going to come up even earlier. But it's still going to resemble. McHale is meant and kinetics. And so, really, the main point here that we're trying to make is that the greater the value of the Alistair constant l not, the more sigmoid all the curve will be Aziz. We see here with this green curve being the most sigmoid all. And so it turns out that amongst all biochemists, there are really two popular models that really explain the sigmoid all kinetics of Alice Derek Enzymes. And so the first model is referred to as the concerted model, also known as the M W C model, which MWC, by the way, are the first letters of the last names of the three scientists that discovered this concerted model and then the second model that scientists believe can explain Sig model Kinetics of Alice Derek Enzymes is the sequential model, also known as the K N F model and again K N f are the letters of the last names of the three scientists that discovered the sequential model Now, uh, Mork commonly, uh, these are referred to as the concerted in the sequential model. And so it turns out that in both of these models Alice, Terek enzymes reaction activity are going to be affected by Alice Terek defectors. And so, before we actually get into talking about the details of the concerted model and the sequential model, we're first going to talk about these Alice Terek defectors that can affect the enzymes in both of these models. So in our next lesson video, I'll see you guys where we'll talk more about thes Alice Terek defectors