5d01 | pdb_00005d01

Crystal structure of BshA from B. subtilis complexed with N-acetylglucosaminyl-malate

spinqualitylabelsall models 5d01, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5d01 is a 2 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.02Å Ligands: GMT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BSHA_BACSU Involved in bacillithiol (BSH) biosynthesis. Catalyzes the first step of the pathway, the formation of N-acetylglucosaminylmalate (GlcNAc-Mal) from UDP-N-acetylglucosamine (UDP-GlcNAc) and L-malate. Publication Abstract from PubMed Bacillithiol is a compound produced by several Gram-positive bacterial species, including the human pathogens Staphylococcus aureus and Bacillus anthracis. It is involved in maintaining cellular redox balance as well as the destruction of reactive oxygen species and harmful xenobiotic agents, including the antibiotic fosfomycin. BshA, BshB, and BshC are the enzymes involved in bacillithiol biosynthesis. BshA is a retaining glycosyltransferase responsible for the first committed step in bacillithiol production, namely the addition of N-acetylglucosamine to l-malate. Retaining glycosyltransferases like BshA are proposed to utilize an SNi-like reaction mechanism in which leaving group departure and nucleophilic attack occur on the same face of the hexose. However, significant questions regarding the details of how BshA and similar enzymes accommodate their substrates and facilitate catalysis persist. Here we report X-ray crystallographic structures of BshA from Bacillus subtilis 168 bound with UMP and/or GlcNAc-mal at resolutions of 2.15 and 2.02 A, respectively. These ligand-bound structures, along with our functional and computational studies, provide clearer insight into how BshA and other retaining GT-B glycosyltransferases operate, corroborating the substrate-assisted, SNi-like reaction mechanism. The analyses presented herein can serve as the basis for the design of inhibitors capable of preventing bacillithiol production and, subsequently, help combat resistance to fosfomycin in various pathogenic Gram-positive microorganisms. A Structural, Functional, and Computational Analysis of BshA, the First Enzyme in the Bacillithiol Biosynthesis Pathway.,Winchell KR, Egeler PW, VanDuinen AJ, Jackson LB, Karpen ME, Cook PD Biochemistry. 2016 Aug 23;55(33):4654-65. doi: 10.1021/acs.biochem.6b00472. Epub , 2016 Aug 11. PMID:27454321 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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