3p3l | pdb_00003p3l

Crystal Structure of the Cytochrome P450 monooxygenase AurH (wildtype) from Streptomyces Thioluteus

spinqualitylabelsall models 3p3l, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3p3l is a 2 chain structure with sequence from Streptomyces thioluteus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: CL, EPE, HEM, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AURH_STRTU Bifunctional cytochrome P450 protein involved in the biosynthesis of the antibiotic aureothin, a nitroaryl polyketide metabolite with antifungal, cytotoxic and insecticidal activities (PubMed:15612710, PubMed:18855960). Catalyzes the hydroxylation of luteothin (also called deoxyaureothin), leading to the formation of the intermediate (7R)-7-hydroxydeoxyaureothin, followed by the formation of the aureothin tetrahydrofuran ring, the final step in the biosynthesis of aureothin (PubMed:15612710, PubMed:18855960, PubMed:21280577). Publication Abstract from PubMed AurH is a unique cytochrome P450 monooxygenase catalyzing the stepwise formation of a homochiral oxygen heterocycle, a key structural and pharmacophoric component of the antibiotic aureothin. The exceptional enzymatic reaction involves a tandem oxygenation process including a regio- and stereospecific hydroxylation, followed by heterocyclization. For the structural and biochemical basis of this unparalleled sequence, four crystal structures of AurH variants in different conformational states and in complex with the P450 inhibitor ancymidol were solved, which represent the first structures of the CYP151A group. Structural data in conjunction with computational docking, site-directed mutagenesis, and chemical analyses unveiled a switch function when recognizing the two substrates, deoxyaureothin and the hydroxylated intermediate, thus allowing the second oxygenation-heterocyclization step. Furthermore, we were able to modify the chemo- and regioselectivity of AurH, yielding mutants that catalyze the regioselective six-electron transfer of a nonactivated methyl group to a carboxylic acid via hydroxyl and aldehyde intermediates. Structural Fine-Tuning of a Multifunctional Cytochrome P450 Monooxygenase.,Zocher G, Richter ME, Mueller U, Hertweck C J Am Chem Soc. 2011 Jan 31. PMID:21280577 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

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