4p77 | pdb_00004p77

Structure of ribB complexed with substrate Ru5P

spinqualitylabelsall models 4p77, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p77 is a 2 chain structure with sequence from Vibrio cholerae O1 biovar El Tor str. N16961. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.04Å Ligands: 5RP, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RIBB_VIBCH Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate. Publication Abstract from PubMed Riboflavin biosynthesis pathway has been shown to be essential in many pathogens and is absent in humans. Therefore, enzymes involved in riboflavin synthesis are considered as potential antibacterial drug targets. The enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes one of the two committed steps in riboflavin pathway and converts D-ribulose-5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate and formate. Moreover, DHBPS is shown to be indispensable for Mycobacterium, Salmonella and Helicobacter species. Despite the essentiality of this enzyme in bacteria, no inhibitor has been identified hitherto. Here, we describe kinetic and crystal structure characterization of DHBPS from Vibrio cholerae (vDHBPS) with a competitive inhibitor 4-phospho-D-erythronohydroxamic acid (4PEH) at 1.86 A resolution. In addition, we also report the structural characterization of vDHBPS in its apo form, in complex with its substrate and substrate plus metal ions, at 1.96 A, 1.59 A and 2.04 A resolution, respectively. Comparison of these crystal structures suggests that 4PEH inhibits catalytic activity of DHBPS as it is unable to form a proposed intermediate which is crucial for DHBPS activity. Furthermore, vDHBPS structures complexed with substrate and metal ions reveal that unlike Candida albicans, binding of substrate to vDHBPS induces a conformational change from open to closed conformation. Interestingly, the position of second metal ion which is different from Methanococcus jannaschii strongly supports an active role in the catalytic mechanism. Thus, the kinetic and structural characterization of vDHBPS reveal the molecular mechanism of inhibition shown by 4PEH and it can be explored further for designing of novel antibiotics. Structural Basis for Competitive Inhibition of 3,4-Dihydroxy-2-Butanone-4-Phosphate Synthase from Vibrio cholerae.,Islam Z, Kumar A, Singh S, Salmon L, Karthikeyan S J Biol Chem. 2015 Mar 18. pii: jbc.M114.611830. PMID:25792735 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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