New catalytic mechanism for human purine nucleoside phosphorylase

Author(s)

Azevedo Jr, Walter Filgueira de ^[1] ; Canduri, Fernanda ; Fadel, Valmir ; Basso, Luiz Augusto ; Palma, Mário Sérgio ; Santos, Diógenes Santiago

Affiliation

^[1] Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. Instituto de Biociências, Letras e Ciências Exatas. Departamento de Física - Brasil

• Document type: Journal article
• Source: Biochemical and Biophysical Research Communications; v. 327, n. 3, p. 646-649, Feb. 2005.
• Field of knowledge: Biological Sciences - Biophysics

Abstract

Human purine nucleoside phosphorylase has been submitted to intensive structure-based design of inhibitors, most of them using low-resolution structures of human PNP. Recently, several structures of human PNP have been reported, which allowed redefinition of the active site and understanding of the structural basis for inhibition of PNP by acyclovir and immucillin-H. Based on previously solved human PNP structures, we proposed here a new catalytic mechanism for human PNP, which is supported by crystallographic studies and explains previously determined kinetic data. (AU)

• FAPESP's process: 01/07532-0 - Structural genomics of cyclin dependent kinases and plant defensive proteinases and their natural inhibitors
• Grantee: Walter Filgueira de Azevedo Junior
• Support Opportunities: Regular Research Grants