5k9g

Crystal Structure of GTP Cyclohydrolase-IB with Tris

spinqualitylabelsall models 5k9g, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k9g is a 2 chain structure with sequence from Neisseria gonorrhoeae FA 1090. This structure supersedes the now removed PDB entry 3d1t. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: EDO, FMT, SNC, TRS, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GCH4_NEIG1 Converts GTP to 7,8-dihydroneopterin triphosphate. Publication Abstract from PubMed Guanosine 5'-triphosphate (GTP) cyclohydrolase-I (GCYH-I) catalyzes the first step in folic acid biosynthesis in bacteria and plants, biopterin biosynthesis in mammals, and the biosynthesis of 7-deazaguanosine-modified tRNA nucleosides in bacteria and archaea. The type IB GCYH (GCYH-IB) is a prokaryotic-specific enzyme found in many pathogens. GCYH-IB is structurally distinct from the canonical type IA GCYH involved in biopterin biosynthesis in humans and animals, and thus is of interest as a potential antibacterial drug target. We report kinetic and inhibition data of Neisseria gonorrhoeae GCYH-IB and two high-resolution crystal structures of the enzyme; one in complex with the reaction intermediate analog and competitive inhibitor 8-oxoguanosine 5'-triphosphate (8-oxo-GTP), and one with a tris(hydroxymethyl)aminomethane molecule bound in the active site and mimicking another reaction intermediate. Comparison with the type IA enzyme bound to 8-oxo-GTP (guanosine 5'-triphosphate) reveals an inverted mode of binding of the inhibitor ribosyl moiety and, together with site-directed mutagenesis data, shows that the two enzymes utilize different strategies for catalysis. Notably, the inhibitor interacts with a conserved active-site Cys149, and this residue is S-nitrosylated in the structures. This is the first structural characterization of a biologically S-nitrosylated bacterial protein. Mutagenesis and biochemical analyses demonstrate that Cys149 is essential for the cyclohydrolase reaction, and S-nitrosylation maintains enzyme activity, suggesting a potential role of the S-nitrosothiol in catalysis. Mechanism and catalytic strategy of the prokaryotic-specific GTP cyclohydrolase-IB.,Paranagama N, Bonnett SA, Alvarez J, Luthra A, Stec B, Gustafson A, Iwata-Reuyl D, Swairjo MA Biochem J. 2017 Mar 7;474(6):1017-1039. doi: 10.1042/BCJ20161025. PMID:28126741 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cyclohydrolase 3D structures

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