6mp8

X-ray crystal structure of VioC bound to Fe(II), D-arginine, and 2-oxoglutarateX-ray crystal structure of VioC bound to Fe(II), D-arginine, and 2-oxoglutarate

Structural highlights 6mp8 is a 1 chain structure with sequence from Streptomyces vinaceus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Activity: Oxidoreductase, with EC number 1.14.11.41 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ARGHX_STRVI] Involved in the biosynthesis of capreomycidine, an unusual amino acid used by non-ribosomal peptide synthases (NRPS) to make the tuberactinomycin class of peptide antibiotics such as viomycin and capreomycin. Catalyzes the stereospecific hydroxylation of the C3 of (2S)-arginine to generate (3S)-hydroxy-(2S)-arginine. Usually clavaminic acid synthase-like oxygenases catalyze the formation of threo diastereomers, however VioC produces the erythro diastereomer of beta-carbon-hydroxylated L-arginine. It exerts a broad substrate specificity by accepting the analogs L-homoarginine and L-canavanine for the beta-carbon hydroxylation. Publication Abstract from PubMed When challenged with substrate analogues, iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases can promote transformations different from those they enact upon their native substrates. We show here that the Fe/2OG enzyme, VioC, which is natively an l-arginine 3-hydroxylase, catalyzes an efficient oxidative deamination of its substrate enantiomer, d-Arg. The reactant complex with d-Arg retains all interactions between enzyme and substrate functional groups, but the required structural adjustments and opposite configuration of C2 position this carbon more optimally than C3 to donate hydrogen (H(*)) to the ferryl intermediate. The simplest possible mechanism, C2 hydroxylation followed by elimination of ammonia, is inconsistent with the demonstrated solvent origin of the ketone oxygen in the product. Rather, the reaction proceeds via a hydrolytically labile C2-iminium intermediate, demonstrated by its reductive trapping in solution with NaB(2)H4 to produce racemic [(2)H]Arg. Of two alternative pathways to the iminium species, C2 hydroxylation followed by dehydration versus direct desaturation, the latter possibility appears to be more likely, because the former mechanism would be expected to result in detectable incorporation of (18)O from (18)O2. The direct desaturation of a C-N bond implied by this analysis is analogous to that recently posited for the reaction of the l-Arg 4,5-desaturase, NapI, thus lending credence to the prior mechanistic proposal. Such a pathway could also potentially be operant in a subset of reactions catalyzed by Fe/2OG N-demethylases, which have instead been purported to enact C-N bond cleavage by methyl hydroxylation and elimination of formaldehyde. alpha-Amine Desaturation of d-Arginine by the Iron(II)- and 2-(Oxo)glutarate-Dependent l-Arginine 3-Hydroxylase, VioC.,Dunham NP, Mitchell AJ, Del Rio Pantoja JM, Krebs C, Bollinger JM Jr, Boal AK Biochemistry. 2018 Nov 20;57(46):6479-6488. doi: 10.1021/acs.biochem.8b00901., Epub 2018 Nov 7. PMID:30403469 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hydroxylases 3D structures

spinqualitylabelsall models 6mp8, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image