Structural features and kinetic characterization of alanine racemase from Bacillus pseudofirmus OF4

被引：8

作者：

Dong, Hui ^{[1
]}

Hu, Tingting ^{[2
]}

He, Guangzheng ^{[3
]}

Lu, Deren ^{[2
]}

Qi, Jianxun ^{[4
]}

Dou, Yanshu ^{[2
]}

Long, Wei ^{[1
]}

He, Xin ^{[1
]}

Ju, Jiansong ^{[3
]}

Su, Dan ^{[2
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Inst Radiat Med, Key Lab Tianjin Radiat & Mol Nucl Med, Tianjin, Peoples R China

[2] Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China

[3] Hebei Normal Univ, Coll Life Sci, Shijiazhuang, Hebei, Peoples R China

[4] Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 497卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Alanine racemase; Bacillus pseudofirmus; Substrate entryway; Dimerization; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; X-RAY; PURIFICATION; ENZYME; RESOLUTION; CONTAINS; ENTRYWAY;

D O I：

10.1016/j.bbrc.2018.02.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alanine racemase (Alr) is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes a reversible racemization between the enantiomers of alanine. D-Alanine is an indispensable constituent in the biosynthesis of bacterial cell-wall peptidoglycan, and its inhibition is lethal to prokaryotes, which makes it an attractive target for designing antibacterial drugs. In this study, the molecular structure of alanine racemase from Bacillus pseudofirmus OF4 (DadX(OF4)) was determined by X-ray crystallography to a resolution of 1.8 angstrom. The comparison of DadX(OF4) with alanine racemases from other bacteria demonstrated a conserved overall fold. Enzyme kinetics analysis showed that the conserved residues at the substrate entryway and the salt bridge at the dimer interface are critical for enzyme activity. These structural and biochemical findings provide a template for future structure-based drug-development efforts targeting alanine racemases. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：139 / 145

页数：7

共 31 条

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