Transition state analogue discrimination by related purine nucleoside phosphorylases

Erika A. Taylor Ringia; Peter C. Tyler; Gary B. Evans; Richard H. Furneaux; Andrew S. Murkin; Vern L. Schramm

doi:10.1021/ja061403n

Transition state analogue discrimination by related purine nucleoside phosphorylases

Erika A. Taylor Ringia, Peter C. Tyler, Gary B. Evans, Richard H. Furneaux, Andrew S. Murkin, Vern L. Schramm

Biochemistry

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English (US)
Pages (from-to)	7126-7127
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	128
Issue number	22
DOIs	https://doi.org/10.1021/ja061403n
State	Published - Jun 7 2006

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja061403n

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AU - Taylor Ringia, Erika A.

AU - Tyler, Peter C.

AU - Evans, Gary B.

AU - Furneaux, Richard H.

AU - Murkin, Andrew S.

AU - Schramm, Vern L.

PY - 2006/6/7

Y1 - 2006/6/7

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AB - 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.

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Transition state analogue discrimination by related purine nucleoside phosphorylases

Abstract

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