Lesson 3 – Video 2
1190 [00:00:00.86] SPEAKER 1: Hi. In this video, we'd like to continue discussing enzymes.
1191 particular, we want to focus on the mechanisms whereby an enzyme will reduce the
1192 energy of a reaction.And then we'll end up talking a little bit about protein folding.
1193 [00:00:18.04] In this first slide, we see in blue an enzyme called lysozyme which acts
1194 polysaccharides which are strings of sugars which are shown in red. The reaction
1195 longer polysaccharide into two smaller fragments.And here you can see some of the
1196 have a glycocidic bond between two sugar molecules. You have two amino acids--
1197 and aspartic acid-- making a simultaneous attacks on the glycosidic bond proceeding to
1198 covalent intermediate with this sugar.
1199 [00:01:04.10] And then we have hydrolysis of a water molecule adding a proton to the
1200 acid and putting a hydroxyl group on the carbon cleaving this ester bond which is an
1201 intermediate.And that's pretty nice, but I feel it's still fairly complicated.And so I'd like
1202 build your intuition about a kind of enzyme mechanism.And really the only rule you
1203 know is that opposite charges attract, like charges repel.
1204 [00:01:38.26] This figure from the book shows three mechanisms of enzyme catalysis.
1205 is undeniably important. It's simply an enzyme which will hold the reactants in the
1206 orientation near each other, giving them plenty of time to react and not relying on
1207 interactions, collisions in solution based on diffusion.
1208 [00:02:03.94] The second mechanism is one we'll talk about more, and that is electronic
1209 stabilization of the transition state. However, this picture is somewhat flawed as you
don't see a
1210 transition state. You have a charged molecule. What you see is electronic stabilization of
1211 molecule itself.And we'll talk about that.
1212 [00:02:24.54] And finally, I think I disagree with this third mechanism of physically
1213 or bending a molecule, but perhaps I don't understand exactly what they're talking
about. So now
1214 we'll talk more about mechanism two and we'll also use that to discuss some features of
1215 structure in a little greater detail.
1216 [00:02:46.14] Now let's talk a little bit more about an amino acid. In solution, we've
talked about 1217 it being a zwitterion with a positively charged amino group and a negatively charged
group. And here is a peptide bond with the C-alpha carbon, 1218 another amino group here
1219 another carboxyl end here. If we look along these four atoms in the peptide bond,
1220 a fairly significant dipole moment where we have excess electron density at the oxygen
1221 relative electron deficiency at the proton. So that results in a dipole moment of about
1222 which is quite large.
1223 [00:03:37.99] And I should just mention that-- for whatever reason, who knows-- in
1224 convention is different from physics. In biology, the arrow points towards the positive
end of the
1225 dipole. That's opposite what you may have learned in physics class.
1226 [00:03:54.76] So now I'm going to talk about what happens to those dipole moments for
1227 these peptide bonds in the helix. Unfortunately, the orientation is upside down here. But
1228 have for those hydrogen bonds, if we can look, here is a peptide bond. We have the
1229 alpha carbon, the amino group, the hydrogen.And so we have, in this case, a dipole, but
1230 pointing almost along the alpha helix axis.And we can see many of those. Here's
1231 pointing up. Here's another one.
1232 [00:04:38.67] Now in this slide, it's emphasizing all the different dipole moment of the
1233 individual peptide bonds or amino acids, however you want to think about it.And these
1234 into a fairly significant vector that points down the alpha helix. This has the effect of
1235 fairly significant electric fields at either end of the alpha helix.
1236 [00:05:02.78] Now let's imagine a hypothetical active site where there's going to be a
1237 reacting in here.And we have four alpha helices lined up pointing towards the active
site. It's not
1238 at all unusual to have this sort of orientation, although, it would be spread out in three
1239 dimensions rather than in two.
1240 [00:05:24.98] Now to understand a little bit more about the stabilization of the
1241 we need to think about a molecule in a generic transition state.And I've just drawn a
1242 with five atoms here, and we're going to pretend that this enzyme is going to cleave
1243 bond three and four.As it goes towards the transition state, so here's the starting
1244 bond between three and four. Here is the product, a broken bond between three and
four.And the 1245 transition state is starting to stretch bond three and four longer and longer on its way to
1247 [00:06:05.00] Because you have a certain amount of electron density between atoms
1248 four, stretching it out over a longer distance means there's going to be less electron
density in the
1249 transition state relative t