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.
Related Concept Videos
Induced-fit Model
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
Enzymes
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Peptide Bonds
Ligand Binding and Linkage
Introduction to Mechanisms of Enzyme Catalysis
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...


