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PLoS One. 2017 Jan 20;12(1):e0170202. doi: 10.1371/journal.pone.0170202. eCollection 2017.

Delineating Substrate Diversity of Disparate Short-Chain Dehydrogenase Reductase from Debaryomyces hansenii.

Author information

1
Biomoneta Research Private Limited, Bangalore, India.
2
Centre for Cellular and Molecular Platforms (C-CAMP), National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
3
Bugworks Research India Private Limited, Bangalore, India.
4
Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata, India.

Abstract

Short-chain dehydrogenase reductases (SDRs) have been utilized for catalyzing the reduction of many aromatic/aliphatic prochiral ketones to their respective alcohols. However, there is a paucity of data that elucidates their innate biological role and diverse substrate space. In this study, we executed an in-depth biochemical characterization and substrate space mapping (with 278 prochiral ketones) of an unannotated SDR (DHK) from Debaryomyces hansenii and compared it with structurally and functionally characterized SDR Synechococcus elongatus. PCC 7942 FabG to delineate its industrial significance. It was observed that DHK was significantly more efficient than FabG, reducing a diverse set of ketones albeit at higher conversion rates. Comparison of the FabG structure with a homology model of DHK and a docking of substrate to both structures revealed the presence of additional flexible loops near the substrate binding site of DHK. The comparative elasticity of the cofactor and substrate binding site of FabG and DHK was experimentally substantiated using differential scanning fluorimetry. It is postulated that the loop flexibility may account for the superior catalytic efficiency of DHK although the positioning of the catalytic triad is conserved.

PMID:
28107498
PMCID:
PMC5249140
DOI:
10.1371/journal.pone.0170202
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Arindam Ghatak and Janani Venkatraman are employed with Biomoneta Research Private Limited, Bangalore, India. Anirudh P Shanbhag and Santanu Datta are employed with Bugworks Research India Private Limited. This does not alter authors’ adherence to PLOS ONE policies on sharing data and materials.

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