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Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue96 in the Plasmodial Enzyme

Pareek, Vidhi and Samanta, Moumita and Joshi, Niranjan V and Balaram, Hemalatha and Murthy, Mathur RN and Balaram, Padmanabhan (2016) Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue96 in the Plasmodial Enzyme. In: CHEMBIOCHEM, 17 (7). pp. 620-629.

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Official URL: http://dx.doi.org/10.1002/cbic.201500532

Abstract

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residuephenylalanineat this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the WILEY-V C H VERLAG GMBH, POSTFACH 101161, 69451 WEINHEIM, GERMANY
Keywords: enzyme catalysis; isomerization; sequence conservation; structure-activity relationships; triosephosphate isomerase
Department/Centre: Division of Biological Sciences > Centre for Ecological Sciences
Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 11 May 2016 06:13
Last Modified: 11 May 2016 06:13
URI: http://eprints.iisc.ac.in/id/eprint/53777

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