4rl4

Crystal structure of GTP cyclohydrolase II from Helicobacter pylori 26695

spinqualitylabelsall models 4rl4, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rl4 is a 2 chain structure with sequence from Campylobacter pylori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PPV Related: 2bz0, 4i14 Gene: HP_0802, ribA (Campylobacter pylori) Activity: GTP cyclohydrolase II, with EC number 3.5.4.25 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RIBA_HELPY] Catalyzes the conversion of GTP to 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (DARP), formate and pyrophosphate. Publication Abstract from PubMed GTP cyclohydrolase II (GCHII), catalyzes the conversion of GTP to 2,5-diamino-6-beta-ribosyl-4(3H)-pyrimidinone-5'-phosphate and has been shown to be essential for pathogens. Here we describe the biochemical, kinetic and structural characterization of GCHII from Helicobacter pylori (hGCHII). The crystal structure of hGCHII, unlike other GCHII structures, revealed that cysteines at the active site existed in oxidized state forming two disulfide bonds and lacked Zn2+ that was shown to be indispensable for catalytic activity in other species. However, incubation of hGCHII with hydrogen peroxide, an oxidizing agent, followed by PAR-assay showed that Zn2+ was intrinsically present, indicating that all cysteines at the catalytic site remained in reduced state. Moreover, site directed mutagenesis of catalytic site cysteines revealed that only three, out of four cysteines were essential for hGCHII activity. These results, though, indicated that hGCHII crystallized in oxidized form, the expulsion of Zn2+ upon oxidation of catalytic cysteines revealed its ability to act in response to the redox environment. Exploring further, incubation of hGCHII with reversible thiol modifying agent S-methyl-methane-thiosulfonate resulted in loss of GCHII activity due to oxidation of its cysteine residues as revealed by mass spectrometry studies. However, addition of reducing agent DTT partially restored the hGCHII catalytic activity. Taken together, these results demonstrate that hGCHII can regulate its catalytic activity depending on the redox environment, a function hitherto unknown for GCHII. Structural and biochemical characterization of GTP cyclohydrolase II from Helicobacter pylori reveals its redox dependent catalytic activity.,Yadav S, Karthikeyan S J Struct Biol. 2015 Aug 10. pii: S1047-8477(15)30042-3. doi:, 10.1016/j.jsb.2015.08.004. PMID:26272484 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cyclohydrolase

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