Binding of a possible transition state analogue to the active site of carboxypeptidase A.

Abstract:

:The mode of binding of the competitive inhibitor 2-benzyl-3-formylpropanoic acid to the active site of carboxypeptidase A has been studied by x-ray diffraction methods to a resolution of 1.7 A. The actual species bound to the enzyme was determined to be the gem-diol resulting from covalent hydration at the aldehyde carbonyl. Details relating to the process of association of inhibitor with enzyme are unknown at this time: the free aldehyde could initially bind to the enzyme and subsequently undergo catalytic hydration; or, the hydrate itself could be the species initially binding to the enzyme, because it does exist to a high degree (25%) in aqueous solution. Nevertheless, the structure of the complex reported is reminiscent of a possible tetrahedral intermediate that would be encountered in a general base hydrolytic mechanism. Of course, other mechanistic proposals, such as the anhydride pathway, cannot be ruled out simply on the basis of the structure of this enzyme-inhibitor complex.

authors

Christianson DW,Lipscomb WN

doi

10.1073/pnas.82.20.6840

subject

Has Abstract

pub_date

1985-10-01 00:00:00

pages

6840-4

issue

20

eissn

0027-8424

issn

1091-6490

journal_volume

82

pub_type

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