6d9t

BshA from Staphylococcus aureus complexed with UDP

spinqualitylabelsall models 6d9t, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6d9t is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: UDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A068A5A2_STAAU Publication Abstract from PubMed Bacillithiol is a glucosamine-derived antioxidant found in several pathogenic Gram-positive bacteria. The compound is involved in maintaining the appropriate redox state within the cell as well as detoxifying foreign agents like the antibiotic fosfomycin. Bacillithiol is produced via the action of three enzymes, including BshA, a retaining GT-B glycosyltransferase that utilizes UDP-N-acetylglucosamine and l-malate to produce N-acetylglucosaminyl-malate. Recent studies suggest that retaining GT-B glycosyltransferases like BshA utilize a substrate-assisted mechanism that goes through an SN i-like transition state. In a previous study, we relied on X-ray crystallography as well as computational simulations to hypothesize the manner in which substrates would bind the enzyme, but several questions about substrate binding and the role of one of the amino acid residues persisted. Another study demonstrated that BshA might be subject to feedback inhibition by bacillithiol, but this phenomenon was not analyzed further to determine the exact mechanism of inhibition. Here we present X-ray crystallographic structures and steady-state kinetics results that help elucidate both of these issues. Our ligand-bound crystal structures demonstrate that the active site provides an appropriate steric and geometric arrangement of ligands to facilitate the substrate-assisted mechanism. Finally, we show that bacillithiol is competitive for UDP-N-acetylglucosamine with a Ki value near 120-130 muM and likely binds within the BshA active site, suggesting that bacillithiol modulates BshA activity via feedback inhibition. The work presented here furthers our understanding of bacillithiol metabolism and can aid in the development of inhibitors to counteract resistance to antibiotics such as fosfomycin. A structural and functional analysis of the glycosyltransferase BshA from Staphylococcus aureus: Insights into the reaction mechanism and regulation of bacillithiol production.,Royer CJ, Cook PD Protein Sci. 2019 Jun;28(6):1083-1094. doi: 10.1002/pro.3617. Epub 2019 Apr 24. PMID:30968475 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycosyltransferase 3D structures

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