Exit of products from the active site of human glutathione transferase P1-1 is promoted by valine 10

Authors
Micaloni, C Mazzetti, AP Nuccetelli, M Rossjohn, J McKinstry, WJ Antonini, G Caccuri, AM Oakley, AJ Federici, G Ricci, G Parker, MW Lo Bello, M
Citation
C. Micaloni et al., Exit of products from the active site of human glutathione transferase P1-1 is promoted by valine 10, CHEM-BIO IN, 133(1-3), 2001, pp. 192-195
Citations number
10
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CHEMICO-BIOLOGICAL INTERACTIONS
ISSN journal
00092797 → ACNP
Volume
133
Issue
1-3
Year of publication
2001
Pages
192 - 195
Database
ISI
SICI code
0009-2797(20010228)133:1-3<192:EOPFTA>2.0.ZU;2-J
Abstract
search of potential residues involved in co-substrate recognition or produc t dissociation we have probed the electrophilic binding site (H-site) of hu man placental glutathione transferase (GST P1-1) by mutating two valines (V al 10 and Val 35) into glycine and alanine, respectively. The results demon strate that Val35Ala behaves similar to wild type, whereas Val10Gly exhibit s a strong decrease of k(cat) towards two selected co-substrates, ethacryni c acid and 1-chloro-2,4-dinitrobenzene. Kinetic, spectroscopic and crystall ographic analysis of the Val10Gly mutant enzyme indicate that Val 10, locat ed on the floor of the H-site, may orient products and help them to leave t he active site. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.