(Modeling proteins) (Chymotrypsin Mechanism: Step 1, Step 2, Step 3, Step 4, Step 5, Step 6)
After the peptide bund is broken, the amine fragment, here CH3-NH2, migrates out of the active site. This leaves behind an ester composed of Ser195 reacting with Trp252. A water molecule now reacts with this ester, adding a hydroxyl group to the carboxylic carbon, forming a tetrahedral carbon again. At the same time, the proton adds to His57 to form histidinium again. (PDB file) (ARC file)
(A) This is a predicted intermediate. There is no mention of it in the literature, so it should be regarded as a new idea, and therefore viewed with some skepticism.
(B) The carbonyl carbon of Trp252 now has a tetrahedral coordination once more. In place of the weakened peptide bond, there is now the hydroxyl group from the water that will be used in the hydrolysis. As with the earlier tetrahedral intermediate, the carbonyl oxygen has a formal charge of -1.
|
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 |