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Molecular docking and molecular dynamics simulations of fumarate hydratase and its mutant H235N complexed with pyromellitic acid and citrate

Subasri, S and Chaudhary, Santosh Kumar and Sekar, K and Kesherwani, Manish and Velmurugan, D (2017) Molecular docking and molecular dynamics simulations of fumarate hydratase and its mutant H235N complexed with pyromellitic acid and citrate. In: JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, 15 (6).

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Official URL: http://dx.doi.org/ 10.1142/S0219720017500263

Abstract

Fumarase catalyzes the reversible, stereospecific hydration/dehydration of fumarate to L-malate during the Kreb's cycle. In the crystal structure of the tetrameric fumarase, it was found that some of the active site residues S145, T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with pyromellitic acid and citrate which help to the protonation state for the conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water-mediated interactions were lost due to the shifting of active site water molecule by 0.7 angstrom away. Molecular dynamics (MD) simulations were also carried out by NAMD and analyzed using Assisted Model Building with Energy Refinement (AMBER) program to better understand the conformational stability and other aspects during the binding of pyromellitic acid and citrate with native and mutant FH. The role of hydrogen bonds and hydrophobic interactions was also analyzed. The present study confirms that the H235N mutation has a major effect on the catalytic activity of fumarase which is evident from the biochemical studies.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the IMPERIAL COLLEGE PRESS, 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND
Department/Centre: Division of Physical & Mathematical Sciences > Physics
Depositing User: review EPrints Reviewer
Date Deposited: 13 Jan 2018 06:44
Last Modified: 13 Jan 2018 06:44
URI: http://eprints.iisc.ac.in/id/eprint/58593

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