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

Joubert, F Neitz, AWH Louw, AI

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

31

INGLESE

Article

Biochemistry & Biophysics

PROTEINS-STRUCTURE FUNCTION AND GENETICS

0887-3585 → ACNP

45

2

2001

136 - 143

ISI

0887-3585(20011101)45:2<136:SISAFO>2.0.ZU;2-S

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.