Structure-based inhibitor screening: A family of sulfonated dye inhibitorsfor malaria parasite triosephosphate isomerase

Citation
F. Joubert et al., Structure-based inhibitor screening: A family of sulfonated dye inhibitorsfor malaria parasite triosephosphate isomerase, PROTEINS, 45(2), 2001, pp. 136-143
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
45
Issue
2
Year of publication
2001
Pages
136 - 143
Database
ISI
SICI code
0887-3585(20011101)45:2<136:SISAFO>2.0.ZU;2-S
Abstract
The crystal structure of malaria triosephosphate isomerase (TIM) was screen ed against the National Cancer Institute database of three-dimensional mole cular structures. Ten top-scoring commercially available compounds were ana lyzed for inhibition of recombinant TIM. Two anionic dyes showed inhibition of TIM at concentrations of < 100 mM. Four related sulfonated dyes were id entified from the literature, docked, and screened in vitro. All showed inh ibition of malaria TIM. Models indicate that these compounds bind in two su ggested conformations to the active site region of the TIM enzyme. These co mpounds may be used in rational modification procedures for the synthesis o f lead anti-TIM drugs. (C) 2001 Wiley-Liss, Inc.