(Modeling proteins) (Chymotrypsin Mechanism: Step 1, Step 2, Step 3, Step 4, Step 5, Step 6)
The postulated tetrahedral ester carbon intermediate and histidinium have now decomposed to form a simple acid, alcohol, and histidine, following the migration of the imidazolium proton to Ser195. (PDB file) (ARC file)
(A) This is an expected intermediate.
(B) The carboxylic acid group is held in place by three hydrogen bonds, to His57, Gly193, and Ser195. There is a fourth hydrogen bond, to the departing amine, but as this fragment is highly mobile (it's migrating out of the active site) it cannot exert any mechanical constraining force on the acid.
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Toggle display all Toggle center picture Fit to screen Interesting parts:
Catalytic triad:
Substrate:
Active site plus substrate:
Ser195 forms two bonds with Trp252, first, the ester bond between the hydroxyl oxygen and the carbonyl carbon of Trp252, forming the tetrahedral intermediate, carbon atom 3485, and second, the hydrogen bond between Ser195 peptide hydrogen and Trp252's carbonyl oxygen. Gly193 forms a similar hydrogen bond. Between Gly 193 and Ser195 is the ionized Asp194, which forms a salt bridge with Ile16. Toggle spin Toggle stereo |