Biochemical characterization and redesign of the coenzyme specificity of a novel monofunctional NAD+-dependent homoserine dehydrogenase from the human pathogen Neisseria gonorrhoeae

Tang, Wanggang; Xue, Ding; Meng, Jiang; Feng, Yamin; Xie, Manman; Xu, Haonan; Song, Ping

doi:10.1016/j.pep.2021.105909

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…Therefore, the substrate binding and catalytic residues cannot be identified from the available structural information. Fortunately, computational biology approaches, such as structural modeling, molecular docking, and molecular dynamic simulation, provide powerful tools for predicting substrate or coenzyme binding sites [2,8,9,29,30]. In this work, the three-dimensional structure of NgBDH was first modeled with AlphaFold2, which has an overall structure very similar to those of other members of the MDR family.…”

Section: Discussionmentioning

confidence: 99%

“…Like those of other dehydrogenases [8][9][10], the coenzyme recognition mechanisms pertaining to BDHs from the SDR superfamily have been well documented. Several crystal structures of SDR-type BDHs with bound NAD + are also available, such as meso-BDHs from Klebsiella pneumoniae (Protein Data Bank [PDB] code: 1GEG) [11] and Serratia marcescens (PDB code: 6XEW) [12], and (2 S,3 S)-BDH from Corynebacterium glutamicum (PDB code: 3A28) [5].…”

Section: Introductionmentioning

confidence: 99%

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The critical role of residues Phe120 and Val161 of (2 R,3 R)‑2,3‑butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site‐directed mutagenesis

Dong,

Zhang,

Gui

et al. 2024

J Basic Microbiol

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NAD+‐dependent (2 R,3 R)‑2,3‑butanediol dehydrogenase (BDH) from Neisseria gonorrhoeae (NgBDH) is a representative member of the medium‐chain dehydrogenase/reductase (MDR) superfamily. To date, little information is available on the substrate binding sites and catalytic residues of BDHs from this superfamily. In this work, according to molecular docking studies, we found that conserved residues Phe120 and Val161 form strong hydrophobic interactions with both (2 R,3 R)‑2,3‑butanediol (RR‐BD) and meso‐2,3‑butanediol (meso‐BD) and that mutations of these residues to alanine or threonine impair substrate binding. To further evaluate the roles of these two residues, Phe120 and Val161 were mutated to alanine or threonine. Kinetic analysis revealed that, relative to those of wild type, the apparent KM values of the Phe120Ala mutant for RR‐BD and meso‐BD increased 36‐ and 369‐fold, respectively; the catalytic efficiencies of this mutant with RR‐BD and meso‐BD decreased approximately 586‐ and 3528‐fold, respectively; and the apparent KM values of the Val161Ala mutant for RR‐BD and meso‐BD increased 4‐ and 37‐fold, respectively, the catalytic efficiencies of this mutant with RR‐BD and meso‐BD decreased approximately 3‐ and 28‐fold, respectively. Additionally, the Val161Thr mutant slightly decreased catalytic efficiencies (twofold with RR‐BD; 7.3‐fold with meso‐BD) due to an increase in KM (sixfold for RR‐BD; 24‐fold for meso‐BD) and a slight increase (2.8‐fold with RR‐BD; 3.3‐fold with meso‐BD) in kcat. These findings validate the critical roles of Phe120 and Val161 of NgBDH in substrate binding and catalysis. Overall, the current study provides a better understanding of the substrate binding and catalysis of BDHs within the MDR superfamily.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The critical role of residues Phe120 and Val161 of (2 R,3 R)‑2,3‑butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site‐directed mutagenesis

Dong,

Zhang,

Gui

et al. 2024

J Basic Microbiol

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“…L. plantarum synthesized amino acids including methionine and D-aspartate to resist oxidative stress (Zhai et al, 2020 ; Kajitani et al, 2021 ). Homoserine dehydrogenase and aspartokinase 3 were both involved in the synthesis of L-homoserine, which was the precursor of methionine, and L-homoserine had certain stress resistance (Wei et al, 2019 ; Liu et al, 2020 ; Tang et al, 2021 ). Thus, their marked upregulation increased the ability of the strains to resist oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Mechanism of Lactiplantibacillus plantarum KM1 Under H2O2 Stress by Proteomics Analysis

et al. 2022

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Lactiplantibacillus plantarum KM1 was screened from natural fermented products, which had probiotic properties and antioxidant function. The survival rate of L. plantarum KM1 was 78.26% at 5 mM H2O2. In this study, the antioxidant mechanism of L. plantarum KM1 was deeply analyzed by using the proteomics method. The results demonstrated that a total of 112 differentially expressed proteins (DEPs) were screened, of which, 31 DEPs were upregulated and 81 were downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEPs participated in various metabolic pathways such as pyruvate metabolism, carbon metabolism, trichloroacetic acid cycle, amino acid metabolism, and microbial metabolism in diverse environments. These metabolic pathways were related to oxidative stress caused by H2O2 in L. plantarum KM1. Therefore, the antioxidant mechanism of L. plantarum KM1 under H2O2 stress provided a theoretical basis for its use as a potential natural antioxidant.

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Expression, Purification, and Bioinformatic Prediction of Mycobacterium tuberculosis Rv0439c as a Potential NADP+-Retinol Dehydrogenase

Tang,

Gui,

Zhang

2023

Mol Biotechnol

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Biochemical characterization and redesign of the coenzyme specificity of a novel monofunctional NAD+-dependent homoserine dehydrogenase from the human pathogen Neisseria gonorrhoeae

Cited by 5 publications

References 42 publications

The critical role of residues Phe120 and Val161 of (2 R,3 R)‑2,3‑butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site‐directed mutagenesis

The critical role of residues Phe120 and Val161 of (2 R,3 R)‑2,3‑butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site‐directed mutagenesis

Antioxidant Mechanism of Lactiplantibacillus plantarum KM1 Under H2O2 Stress by Proteomics Analysis

Expression, Purification, and Bioinformatic Prediction of Mycobacterium tuberculosis Rv0439c as a Potential NADP+-Retinol Dehydrogenase

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