Triosephosphate isomerase from Plasmodium falciparum:. the crystal structure provides insights into antimalarial drug design

Sameer, S Velanker and Soumya, S Ray and Rajesh, S Gokhale and Suma, S and Hemalatha, Balaram and Balaram, P and Murthy, MRN (1997) Triosephosphate isomerase from Plasmodium falciparum:. the crystal structure provides insights into antimalarial drug design. In: Structure, 5 (6). pp. 751-761.

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Abstract

Background: Malaria caused by the parasite Plasmodium falciparum is a major public health concern. The parasite lacks a functional tricarboxylic acid cycle, making glycolysis its sole energy source. Although parasite enzymes have been considered as potential antimalarial drug targets, little is known about their structural biology. Here we report the crystal structure of triosephosphate isomerase (TIM) from P. falciparum at 2.2 Angstrom resolution. Results: The crystal structure of P. falciparum TIM (PfTIM), expressed in Escherichia coli, was determined by the molecular replacement method using the structure of trypanosomal TIM as the starting model. Comparison of the PfTIM structure with other TIM structures, particularly human TIM, revealed several differences, In most TIMs the residue at position 183 is a glutamate but in PtTIM it is a leucine, This leucine residue is completely exposed and together with the surrounding positively charged patch, may be responsible for binding TIM to the erythrocyte membrane. Another interesting feature is the occurrence of a cysteine residue at the dimer interface of PfTIM (Cys13), in contrast to human TIM where this residue is a methionine. Finally, residue 96 of human TIM (Ser96), which occurs near the active site, has been replaced by phenylalanine in PfTIM.

Item Type:	Journal Article
Publication:	Structure
Publisher:	Elsevier Science
Additional Information:	Copy right of this article belongs to Elsevier Science.
Keywords:	β barrel; drug design; malaria; Plasmodium falciparum; triosephosphate isomerase.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	30 Apr 2010 05:45
Last Modified:	19 Sep 2010 06:00
URI:	http://eprints.iisc.ac.in/id/eprint/27361

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