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 Citations (Scopus)

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
StatePublished - Jun 7 2006

Fingerprint

Purine-Nucleoside Phosphorylase
Hydroxyl Radical
Conservation
Ligands
Geometry
Substrates
Catalytic Domain
Nucleosides

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Transition state analogue discrimination by related purine nucleoside phosphorylases. / Taylor Ringia, Erika A.; Tyler, Peter C.; Evans, Gary B.; Furneaux, Richard H.; Murkin, Andrew S.; Schramm, Vern L.

In: Journal of the American Chemical Society, Vol. 128, No. 22, 07.06.2006, p. 7126-7127.

Research output: Contribution to journalArticle

Taylor Ringia, Erika A. ; Tyler, Peter C. ; Evans, Gary B. ; Furneaux, Richard H. ; Murkin, Andrew S. ; Schramm, Vern L. / Transition state analogue discrimination by related purine nucleoside phosphorylases. In: Journal of the American Chemical Society. 2006 ; Vol. 128, No. 22. pp. 7126-7127.
@article{790df8a9629d48b9a35bc093b304b74c,
title = "Transition state analogue discrimination by related purine nucleoside phosphorylases",
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.",
author = "{Taylor Ringia}, {Erika A.} and Tyler, {Peter C.} and Evans, {Gary B.} and Furneaux, {Richard H.} and Murkin, {Andrew S.} and Schramm, {Vern L.}",
year = "2006",
month = "6",
day = "7",
doi = "10.1021/ja061403n",
language = "English (US)",
volume = "128",
pages = "7126--7127",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "22",

}

TY - JOUR

T1 - Transition state analogue discrimination by related purine nucleoside phosphorylases

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

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=33744907483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744907483&partnerID=8YFLogxK

U2 - 10.1021/ja061403n

DO - 10.1021/ja061403n

M3 - Article

C2 - 16734442

AN - SCOPUS:33744907483

VL - 128

SP - 7126

EP - 7127

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 22

ER -