Transition State Analogue Discrimination by Related Purine Nucleoside Phosphorylases
- 12 May 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 128 (22), 7126-7127
- https://doi.org/10.1021/ja061403n
Abstract
Transition state analogues of PNP, the Immucillins and DADMe−Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. The inhibitors with or without the hydroxyl and hydroxymethyl groups of the substrate demonstrate that inhibitor geometry mimicking that of the transition state confers binding affinity discrimination. This finding is remarkable since crystallographic analysis indicates complete conservation of active site residues and contacts to ligands in human and bovine PNPs.Keywords
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