Work

Transition State Analogue Discrimination by Related Purine Nucleoside Phosphorylases

Year: 2006

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja061403n

Authors: Erika A. Taylor Ringia, Peter C. Tyler, Gary B. Evans, Richard H. Furneaux, Andrew S. Murkin, Vern L. Schramm

Institutions: Albert Einstein College of Medicine, Industrial Research Limited

Language: English

Topic: Biochemical and Molecular Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases

Awards: Transition State Analysis of Enzymatic Reactions, Transition State Analysis of Enzymatic Reactions, G5016933685, G521541070, G6503813162