Thymidine phosphorylase from Escherichia coli: tight-binding inhibitors as enzyme active-site titrants

Abdul Gbaj; Philip N Edwards; Philip Reigan; Sally Freeman; Mohammed Jaffar; Kenneth T Douglas

doi:10.1080/14756360500424010

Thymidine phosphorylase from Escherichia coli: tight-binding inhibitors as enzyme active-site titrants

J Enzyme Inhib Med Chem. 2006 Feb;21(1):69-73. doi: 10.1080/14756360500424010.

Authors

Abdul Gbaj¹, Philip N Edwards, Philip Reigan, Sally Freeman, Mohammed Jaffar, Kenneth T Douglas

Affiliation

¹ Wolfson Centre for Rational Structure-Based Design of Molecular Diagnostics, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL, UK.

PMID: 16570508
DOI: 10.1080/14756360500424010

Abstract

Thymidine phosphorylase (EC 2.4.2.4) catalyses the reversible phosphorolysis of pyrimidine 2'-deoxynucleosides, forming 2-deoxyribose-1-phosphate and pyrimidine. 5-Chloro-6-(2-imino-pyrrolidin-1-yl)methyl-uracil hydrochloride (TPI, 1) and its 5-bromo analogue (2), 6-(2-amino-imidazol-1-yl)methyl-5-bromo-uracil (3) and its 5-chloro analogue (4) act as tight-binding stoichiometric inhibitors of recombinant E. coli thymidine phosphorylase, and thus can be used as the first active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as substrate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Deoxyuridine / metabolism
Enzyme Inhibitors / pharmacology*
Escherichia coli / enzymology*
Models, Molecular
Protein Binding
Recombinant Proteins / antagonists & inhibitors*
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Substrate Specificity
Thymidine / metabolism
Thymidine Phosphorylase / antagonists & inhibitors*
Thymidine Phosphorylase / chemistry
Thymidine Phosphorylase / metabolism

Substances

Enzyme Inhibitors
Recombinant Proteins
Thymidine Phosphorylase
Thymidine
Deoxyuridine