5hyg

CmlI (peroxo bound state), arylamine oxygenase of chloramphenicol biosynthetic pathway

spinqualitylabelsall models 5hyg, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hyg is a 1 chain structure with sequence from Streptomyces venezuelae ATCC 10712. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.03Å Ligands: FE, PEO, TLA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CMLI_STRVP Involved in chloramphenicol biosynthesis (PubMed:24347692, PubMed:25564306). Catalyzes the six-electron oxidation of an aryl-amine precursor of chloramphenicol (NH2-CAM) to yield the aryl-nitro group of chloramphenicol (CAM) (PubMed:24347692, PubMed:25564306, PubMed:27203126). During catalysis, upon exposure of the diferrous cluster to O(2), ClmI forms an exceptionally long-lived peroxo intermediate (CmlI-peroxo), which reacts with NH2-CAM to form CAM (PubMed:25564306, PubMed:27203126). Publication Abstract from PubMed The diiron cluster-containing oxygenase CmlI catalyzes the conversion of the aromatic amine precursor of chloramphenicol to the nitroaromatic moiety of the active antibiotic. The X-ray crystal structures of the fully active, N-terminally truncated CmlIDelta33 in the chemically reduced Fe2+/Fe2+ state and a cis mu-1,2(eta 1:eta 1)-peroxo complex are presented. These structures allow comparison with the homologous arylamine oxygenase AurF as well as other types of diiron cluster-containing oxygenases. The structural model of CmlIDelta33 crystallized at pH 6.8 lacks the oxo-bridge apparent from the enzyme optical spectrum in solution at higher pH. In its place, residue E236 forms a mu-1,3(eta 1:eta 2) bridge between the irons in both models. This orientation of E236 stabilizes a helical region near the cluster which closes the active site to substrate binding in contrast to the open site found for AurF. A very similar closed structure was observed for the inactive dimanganese form of AurF. The observation of this same structure in different arylamine oxygenases may indicate that there are two structural states that are involved in regulation of the catalytic cycle. Both the structural studies and single crystal optical spectra indicate that the observed cis mu-1,2(eta 1:eta 1)-peroxo complex differs from the mu-eta 1:eta 2-peroxo proposed from spectroscopic studies of a reactive intermediate formed in solution by addition of O2 to diferrous CmlI. It is proposed that the structural changes required to open the active site also drive conversion of the micro-1,2-peroxo species to the reactive form. Crystal structure of CmlI, the arylamine oxygenase from the chloramphenicol biosynthetic pathway.,Knoot CJ, Kovaleva EG, Lipscomb JD J Biol Inorg Chem. 2016 May 26. PMID:27229511 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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