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

Research output: Contribution to journalArticle

32 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 languageEnglish (US)
Pages (from-to)7126-7127
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number22
DOIs
Publication statusPublished - Jun 7 2006

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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