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Functional annotation of putative fadE9 of Mycobacterium tuberculosis as isobutyryl-CoA dehydrogenase involved in valine catabolism

Rani, Nidhi and Hazra, Samannaya and Singh, Amrita and Surolia, Avadhesha (2019) Functional annotation of putative fadE9 of Mycobacterium tuberculosis as isobutyryl-CoA dehydrogenase involved in valine catabolism. In: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 122 . pp. 45-57.

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Official URL: https://doi.org/10.1016/j.ijbiomac.2018.10.040

Abstract

Members of the Acyl-CoA dehydrogenase (ACADs) family of enzymes play a crucial role in cholesterol and steroid catabolism and are widely studied in the oldest known human pathogen, Mycobacterium tuberculosis (Mtb). However, there is a paucity of information on ACADs involved in branched chain amino acid catabolism. Here we characterized one of the putative ACAD enzyme, fadE9, as ``Isobutyryl CoA Dehydrogenase (IBDH)'' using a combined computational and experimental approach, guided by homology modeled structural information, affirming its role in valine catabolism. Multiple sequence alignment and phylogenetic analysis place it in a separate cluster from a recently identified family of alpha(2)beta(2)-heterotetramer ACADs in Mtb, based on the position of the conserved Arg247 and catalytic Glu368 residues. The conserved Arg247 was predicted to play an essential role at the center of H-bonding network of reaction center and was confirmed by the reduced activity of R247K mutant Thus, in addition to the finding of an architecturally distinct alpha(2)beta(2)-heterotetramer among ACADs, these studies also highlight the differences between MtIBDH, fadE9 from the other ACADs that are involved in cholesterol and steroid catabolism of Mtb. (C) 2018 Published by Elsevier B.V.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to ELSEVIER SCIENCE BV
Keywords: Mycobacterium tuberculosis; Valine catabolism; Isobutyryl CoA Dehydrogenase; fadE9
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 12 Feb 2019 04:53
Last Modified: 12 Feb 2019 04:53
URI: http://eprints.iisc.ac.in/id/eprint/61692

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