4kf2 | pdb_00004kf2

Structure of the P4509 BM3 A82F F87V heme domain

spinqualitylabelsall models 4kf2, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kf2 is a 2 chain structure with sequence from Bacillus megaterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HEM, IMD Related: 4kew, 4key, 4kf0 Gene: cyp102A1, cyp102 (Bacillus megaterium) Resources: FirstGlance, OCA, RCSB, PDBsum Function [CPXB_BACME] Functions as a fatty acid monooxygenase. Catalyzes hydroxylation of medium and long-chain fatty acids at omega-1, omega-2 and omega-3 positions, with optimum chain lengths of 12-16 carbons (lauric, myristic, and palmitic acids). The reductase domain is required for electron transfer from NADP to cytochrome P450. Publication Abstract from PubMed Cytochrome P450 monooxygenases (P450s) have enormous potential in the production of oxychemicals, due to their unparalleled regio- and stereoselectivity. The Bacillus megaterium P450 BM3 enzyme is a key model system, with several mutants (many distant from the active site) reported to alter substrate selectivity. It has the highest reported monooxygenase activity of the P450 enzymes, and this catalytic efficiency has inspired protein engineering to enable its exploitation for biotechnologically relevant oxidations with structurally diverse substrates. However, a structural rationale is lacking to explain how these mutations have such effects in the absence of direct change to the active site architecture. Here, we provide the first crystal structures of BM3 mutants in complex with a human drug substrate, the proton pump inhibitor omeprazole. Supported by solution data, these structures reveal how mutation alters the conformational landscape and decreases the free energy barrier for transition to the substrate-bound state. Our data point to the importance of such "gatekeeper" mutations in enabling major changes in substrate recognition. We further demonstrate that these mutants catalyze the same 5-hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 enzyme. Key Mutations Alter the Cytochrome P450 BM3 Conformational Landscape and Remove Inherent Substrate Bias.,Butler CF, Peet C, Mason AE, Voice MW, Leys D, Munro AW J Biol Chem. 2013 Aug 30;288(35):25387-99. doi: 10.1074/jbc.M113.479717. Epub, 2013 Jul 3. PMID:23828198 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450

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