(Modeling proteins) (Chymotrypsin Mechanism: Step 1, Step 2, Step 3, Step 4, Step 5, Step 6)

Step 6: Chymotrypsin Mechanism - Chymotrypsin after ester is hydrolyzed

 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)

Interesting features of the the acid

(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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Interesting parts:
His57 Asp102 Ser189 Gly193 Asp194
Ser195 Ser214 Ser214 Gly216 Ser217
Gly226 Gly250 Ala251 Trp252 Thr253
H2O

Catalytic triad:
His57 Asp102 Ser195

Substrate:
Gly250 Ala251 Trp252 Thr253


Active site plus substrate:
Gly193 Asp194 Ser195 Gly250 Ala251
Trp252 Thr253 H2O


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.

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