(Modeling proteins) (Chymotrypsin Mechanism: Step 1, Step 2, Step 3, Step 4, Step 5, Step 6)
Although the tetrahedral intermediate in the chymotrypsin catalyzes hydrolysis of a peptide bond is a local minimum on the Potential Energy Surface, it should only be regarded as metastable: the peptide C - N bond, at 1.64 Ångstroms, is highly stretched compared to the ~1.38 Ångstroms in a normal peptide bond. At the carbonyl end of the peptide bond is the tetrahedral intermediate, at the other end is a cationic nitrogen atom; together these two structures form a Zwitterion. This highly charged bond can easily break to form an amine and an ester. In the system being modeled here, scission of the peptide bond has occurred, resulting in a tryptophan esterified to Ser195 and an isolated methylamine molecule. (PDB file) (ARC file)
Interesting features
(A) The Zwitterionic labile peptide bond has been broken, giving rise to a simple amine here, representing the protein fragment resulting from scission, and an ester.
(B) There is a water molecule positioned 4.4 Ångstroms from the ester group. This will be used in hydrolyzing the ester group.
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Toggle display all Toggle center picture Fit to screen Interesting parts:
Catalytic triad:
Substrate:
Oxyanion hole plus substrate:
Tetrahedral intermediate:
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. Substrate in Hydrophobic pocket:
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