4Z0S

F96A Mutant of Plasmodium Falciparum Triosephosphate Isomerase

Summary for 4Z0S

• Entry DOI: 10.2210/pdb4z0s/pdb
• Related: 2VFD 2VFE 2VFF 2VFG 2VFH 4YWI 4YXG 4Z0J
• Descriptor: Triosephosphate isomerase, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: tim barrels, beta-alpha barrels, isomerase, glycolysis
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 2
• Total formula weight: 56277.76

Authors

Pareek, V.,Balaram, P.,Murthy, M.R.N. (deposition date: 2015-03-26, release date: 2016-02-03, Last modification date: 2023-11-08)

Primary citation

Pareek, V.,Samanta, M.,Joshi, N.V.,Balaram, H.,Murthy, M.R.N.,Balaram, P.
Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial Enzyme
Chembiochem, 17:620-629, 2016

PubMed 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 position 96 (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 residue--phenylalanine--at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 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.

PubMed: 26762569
DOI: 10.1002/cbic.201500532

Experimental method

X-RAY DIFFRACTION (2.39 Å)