Binding causes the remote [5′-3H]thymidine kinetic isotope effect in human thymidine phosphorylase

Matthew R. Birck; Vern L. Schramm

doi:10.1021/ja0492642

Binding causes the remote [5′-³H]thymidine kinetic isotope effect in human thymidine phosphorylase

Matthew R. Birck, Vern L. Schramm

Biochemistry

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

30 Scopus citations

Abstract

The remote 5′-3H V/K kinetic isotope effect (KIE) observed in human thymidine phosphorylase (6.1%) is significantly larger than can be explained by the reaction chemistry. One hypothesis connects the 5′-³H KIE in purine nucleoside phosphorylase to that enzyme's S_N1transition state. The transition state of thymidine phosphorylase, however, is an S_N2 nucleophilic displacement. Here we report equilibrium binding isotope effects sufficiently large to explain the presence of this substantial KIE in thymidine phosphorylase.

Original language	English (US)
Pages (from-to)	6882-6883
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	126
Issue number	22
DOIs	https://doi.org/10.1021/ja0492642
State	Published - Jun 9 2004

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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abstract = "The remote 5′-3H V/K kinetic isotope effect (KIE) observed in human thymidine phosphorylase (6.1%) is significantly larger than can be explained by the reaction chemistry. One hypothesis connects the 5′-3H KIE in purine nucleoside phosphorylase to that enzyme's SN1transition state. The transition state of thymidine phosphorylase, however, is an SN2 nucleophilic displacement. Here we report equilibrium binding isotope effects sufficiently large to explain the presence of this substantial KIE in thymidine phosphorylase.",

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N2 - The remote 5′-3H V/K kinetic isotope effect (KIE) observed in human thymidine phosphorylase (6.1%) is significantly larger than can be explained by the reaction chemistry. One hypothesis connects the 5′-3H KIE in purine nucleoside phosphorylase to that enzyme's SN1transition state. The transition state of thymidine phosphorylase, however, is an SN2 nucleophilic displacement. Here we report equilibrium binding isotope effects sufficiently large to explain the presence of this substantial KIE in thymidine phosphorylase.

AB - The remote 5′-3H V/K kinetic isotope effect (KIE) observed in human thymidine phosphorylase (6.1%) is significantly larger than can be explained by the reaction chemistry. One hypothesis connects the 5′-3H KIE in purine nucleoside phosphorylase to that enzyme's SN1transition state. The transition state of thymidine phosphorylase, however, is an SN2 nucleophilic displacement. Here we report equilibrium binding isotope effects sufficiently large to explain the presence of this substantial KIE in thymidine phosphorylase.

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Binding causes the remote [5′-³H]thymidine kinetic isotope effect in human thymidine phosphorylase

Abstract

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