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ERIC S. LANDER: What this enzyme is going to do, it does not change the
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final or the beginning energy states.
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They stay exactly the same.
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So it does not change the energetic favorability.
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But what it does do is it does change.
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Instead of that, when the enzyme is present, it's that.
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It becomes much less energetically unfavorable.
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The energetics, it becomes a much happier state.
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How can it be that that unhappy cis-enediol is able to make this
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chemical transition, and it's not so unlikely anymore?
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We don't have to go through this big, energetic barrier because, in fact,
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we're making it more favorable.
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What it's doing is it's lowering the activation barrier.
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It does change the activation barrier.
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It makes that reaction go forward.
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It catalyzes that reaction by lowering the activation barrier.
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How can it do that?
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Yes?
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STUDENT: Changing the steps?
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ERIC S. LANDER: Well, actually it's going to go through the
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same chemical steps.
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But--
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STUDENT: --changing the shape?
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ERIC S. LANDER: Well, what it can do is it can gently cradle that molecule,
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and by making bonds to it--
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I mean, this is very nurturing kind of picture here's of an enzyme, right--
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it's going to make bonds to it.
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And you're going to get favorable bonds.
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And that's alone enough to lower the activation energy, by stabilizing that
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unstable state, by nuzzling up against it.
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In fact, if that enzyme--
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that enzyme is a protein, so let's give it some structure.
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I'm not going to fuss much about the structure right now-- but maybe it's
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going to have a little pocket in here.
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And what that pocket will do is match, best of all, not G3P and not DHAP, but
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cis-enediol.
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If it is most favorable to that transition state in the way it binds
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the transition state, it stabilizes the transition state, and makes it
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less difficult to be cis-enediol.
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So that's what goes on.
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Enzymes stabilize that transition state.
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They stabilize the transition state.
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Not only that, I told you that if you made it into the transition state, you
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had another problem.
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What fate might befall our poor cis-enediol in the transition state?
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STUDENT: Phosphate--
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STUDENT: The phosphate--
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ERIC S. LANDER: --phosphate comes off.
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So maybe this enzyme might try to prevent that side reaction, too.
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Stabilize the transition state.
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That's job number one for our nice enzyme here, triose phosphate
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isomerase, or just TIM.
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So TIM is cradling this to stabilize the transition state.
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And TIM is going to prevent the side reaction of losing that phosphate.
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Tough job.
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But it does it very well.
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When TIM does its job, because the activation energy is no longer so big
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but is so big, this reaction proceeds much faster.
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It could happen on its own.
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But it's so unlikely, I told you.
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When TIM lowers that activation barrier, do you know how
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much faster it goes?
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It goes, it speeds up, it speeds the reaction by a factor of
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10 to the 10th fold.
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10 to the 10th, do you have a good sense of what 10 to the 10th is?
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10 to the 10th is the difference between one
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second and three centuries.
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I'll be there in a second, or I'll be there in three centuries--
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[LAUGHTER]
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ERIC S. LANDER: --is 10 to the 10th.
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That's a very impressive speedup in a reaction, isn't it?
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It accomplishes this by making it much less unlikely that it gets up there
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and goes down.
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It gets there about 10 to the 10th-fold faster every single time.
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In fact, this is such an amazing enzyme that the rate-limiting step--
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what prevents triose phosphate isomerase from working any faster--
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is not triose phosphate isomerase itself.
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It Is the rate at which molecules diffuse to it.
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It is limited by diffusion.
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It's a diffusion-limited enzyme.
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In fact, as soon as a molecule manages to diffuse to it, poof, it's done.
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It's what's called kinetically perfect as an enzyme.
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There'd be no point in evolution trying to improve this enzyme, because
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it can't go any faster, because it can't get stuff
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any faster by diffusion.
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It is a perfect enzyme.
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TIM is perfect.
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A couple of minutes ago, I told you that triose phosphate isomerase is a
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perfect enzyme.
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Write down in your own words what you think it means when I
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say, perfect enzyme.
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