Specific residues and conformational plasticity define the substrate specificity of short-chain dehydrogenases/reductases.

Autor:	Qian L; Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, USA., Mohanty P; Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, USA., Jayaraman A; Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, USA; Department of Biomedical Engineering, Texas A&M University, College Station, USA., Mittal J; Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, USA; Department of Chemistry, Texas A&M University, College Station, USA; Interdisciplinary Graduate Program in Genetics and Genomics, Texas A&M University, College Station, USA., Zhu X; Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, USA; Interdisciplinary Graduate Program in Genetics and Genomics, Texas A&M University, College Station, USA. Electronic address: xjzhu@tamu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Jan; Vol. 300 (1), pp. 105596. Date of Electronic Publication: 2023 Dec 23.
DOI:	10.1016/j.jbc.2023.105596
Abstrakt:	Short-chain dehydrogenases/reductases (SDRs) are one of the most prevalent enzyme families distributed among the sequenced microorganisms. Despite the presence of a conserved catalytic tetrad and high structural similarity, these enzymes exhibit different substrate specificities. The insufficient knowledge regarding the amino acids underlying substrate specificity hinders the understanding of the SDRs' roles in diverse and significant biological processes. Here, we performed bioinformatic analysis, molecular modeling, and mutagenesis studies to identify the key residues that regulate the substrate specificities of two homologous microbial SDRs (i.e., DesE and KduD). Further, we investigated the impact of altering the physicochemical properties of these amino acids on enzyme activity. Interestingly, molecular dynamics simulations also suggest a critical role of enzyme conformational flexibility in substrate recognition and catalysis. Overall, our findings improve the understanding of microbial SDR substrate specificity and shed light on future rational design of more efficient and effective biocatalysts. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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