Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects

Andrew S. Murkin, Peter C. Tyler, Vern L. Schramm

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The binding of [5′-3H]inosine to human purine nucleoside phosphorylase results in an equilibrium binding isotope effect (BIE) of 1.5%, and transition state formation causes an intrinsic KIE of 4.7%. These values reflect atomic vibrational distortions in the 5′-C-H bonds upon formation of the Michaelis complex and transition state. The degree of atomic distortion for catalysis is compared to that for binding of transition state analogues. Similar radiolabeled forms of the transition-state analogues ImmH and DADMe-ImmH gave large 5′-3H BIEs of 12.6% and 29.2%, respectively. Greater bond distortions occur upon complex formation with transition-state analogues, supporting weaker distortional forces at the transition state than in the formation of complexes with transition-state analogues.

Original languageEnglish (US)
Pages (from-to)2166-2167
Number of pages2
JournalJournal of the American Chemical Society
Volume130
Issue number7
DOIs
StatePublished - Feb 20 2008

Fingerprint

Purine-Nucleoside Phosphorylase
Inosine
Catalysis
Isotopes
Nucleosides

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects. / Murkin, Andrew S.; Tyler, Peter C.; Schramm, Vern L.

In: Journal of the American Chemical Society, Vol. 130, No. 7, 20.02.2008, p. 2166-2167.

Research output: Contribution to journalArticle

@article{f2850a8b1f6d47759f205e27a70607a5,
title = "Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects",
abstract = "The binding of [5′-3H]inosine to human purine nucleoside phosphorylase results in an equilibrium binding isotope effect (BIE) of 1.5{\%}, and transition state formation causes an intrinsic KIE of 4.7{\%}. These values reflect atomic vibrational distortions in the 5′-C-H bonds upon formation of the Michaelis complex and transition state. The degree of atomic distortion for catalysis is compared to that for binding of transition state analogues. Similar radiolabeled forms of the transition-state analogues ImmH and DADMe-ImmH gave large 5′-3H BIEs of 12.6{\%} and 29.2{\%}, respectively. Greater bond distortions occur upon complex formation with transition-state analogues, supporting weaker distortional forces at the transition state than in the formation of complexes with transition-state analogues.",
author = "Murkin, {Andrew S.} and Tyler, {Peter C.} and Schramm, {Vern L.}",
year = "2008",
month = "2",
day = "20",
doi = "10.1021/ja7104398",
language = "English (US)",
volume = "130",
pages = "2166--2167",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects

AU - Murkin, Andrew S.

AU - Tyler, Peter C.

AU - Schramm, Vern L.

PY - 2008/2/20

Y1 - 2008/2/20

N2 - The binding of [5′-3H]inosine to human purine nucleoside phosphorylase results in an equilibrium binding isotope effect (BIE) of 1.5%, and transition state formation causes an intrinsic KIE of 4.7%. These values reflect atomic vibrational distortions in the 5′-C-H bonds upon formation of the Michaelis complex and transition state. The degree of atomic distortion for catalysis is compared to that for binding of transition state analogues. Similar radiolabeled forms of the transition-state analogues ImmH and DADMe-ImmH gave large 5′-3H BIEs of 12.6% and 29.2%, respectively. Greater bond distortions occur upon complex formation with transition-state analogues, supporting weaker distortional forces at the transition state than in the formation of complexes with transition-state analogues.

AB - The binding of [5′-3H]inosine to human purine nucleoside phosphorylase results in an equilibrium binding isotope effect (BIE) of 1.5%, and transition state formation causes an intrinsic KIE of 4.7%. These values reflect atomic vibrational distortions in the 5′-C-H bonds upon formation of the Michaelis complex and transition state. The degree of atomic distortion for catalysis is compared to that for binding of transition state analogues. Similar radiolabeled forms of the transition-state analogues ImmH and DADMe-ImmH gave large 5′-3H BIEs of 12.6% and 29.2%, respectively. Greater bond distortions occur upon complex formation with transition-state analogues, supporting weaker distortional forces at the transition state than in the formation of complexes with transition-state analogues.

UR - http://www.scopus.com/inward/record.url?scp=39549099106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39549099106&partnerID=8YFLogxK

U2 - 10.1021/ja7104398

DO - 10.1021/ja7104398

M3 - Article

VL - 130

SP - 2166

EP - 2167

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 7

ER -