期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 97, 期 -, 页码 106-114出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2016.12.082
关键词
Acinetobacter baumannii; UDP-N-Acetylglucosamine enolpyruvyl transferase; Fosfomycin; Molecular dynamic simulation; Homology modeling
资金
- Department of Science and Technology [INT/RUS/RFBR/P-200]
- University Grant Commission Govt of India [F.6-9/2016(IC)]
- UGC, New Delhi, India
Peptidoglycan (PG) is the key component of the bacterial cell wall. The enzyme UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridinediphospho-N-acetylglucosamine (UNAG), which is the first committed step of PG biosynthesis. Here, we present the biochemical and structural features of the MurA enzyme of the opportunistic pathogen Acinetobacter baumannii (AbMurA). The recombinant AbMurA exists as a monomer in solution and shows optimal activity at pH 7.5 and 37 degrees C. The Km for UDP-N-acetylglucosamine was 1.062 +/- 0.09 mM and for PEP was 1.806 +/- 0.23 mM. The relative enzymatic activity was inhibited similar to 3 fold in the presence of 50 mM fosfomycin (FFQ). Superimposition of the AbMurA model with E. coli demonstrated key structural similarity in the FFQ-binding site. AbMurA also has a surface loop that contains the active site Cys116 that interact with FFQ Sequence analysis indicates the presence of the five conserved amino acids, i.e., K22, C116, D306, D370 and 1371, required for the functional activity like other MurA enzymes from different bacteria. MurA enzymes are indispensable for cell integrity and their lack of counterparts in eukaryotes suggests them to be a promising drug target. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据