4ego

The X-ray crystal structure of CYP199A4 in complex with indole-6-carboxylic acid

spinqualitylabelsall models 4ego, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ego is a 4 chain structure with sequence from Rhodopseudomonas palustris HaA2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.76Å Ligands: 1F1, CL, GOL, HEM, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2IU02_RHOP2 Publication Abstract from PubMed The cytochrome P450 enzyme CYP199A4, from Rhodopseudomonas palustris HaA2, can efficiently demethylate 4-methoxybenzoic acid. It is also capable of oxidising a range of other related substrates. By investigating substrates with different substituents and ring systems we have been able to show that the carboxylate group and the nature of the ring system and the substituent are all important for optimal substrate binding and activity. The structures of the veratric acid, 2-naphthoic acid and indole-6-carboxylic acid substrate-bound CYP199A4 complexes reveal the substrate binding modes and the side-chain conformational changes of the active site residues to accommodate these larger substrates. They also provide a rationale for the selectivity of product oxidation. The oxidation of alkyl substituted benzoic acids by CYP199A4 is more complex, with desaturation reactions competing with hydroxylation activity. The structure of 4-ethylbenzoic acid-bound CYP199A4 revealed that the substrate is held in a similar position to 4-methoxybenzoic acid, and that the C(beta) C-H bonds of the ethyl group are closer to the heme iron than those of the C(alpha) (3.5 vs. 4.8 A). This observation, when coupled to the relative energies of the reaction intermediates, indicates that the positioning of the alkyl group relative to the heme iron may be critical in determining the amount of desaturation that is observed. By mutating a single residue in the active site of CYP199A4 (Phe185) we were able to convert the enzyme into a 4-ethylbenzoic acid desaturase. Investigation of the substrate range of CYP199A4: modification of the partition between hydroxylation and desaturation activities by substrate and protein engineering.,Bell SG, Zhou R, Yang W, Tan AB, Gentleman AS, Wong LL, Zhou W Chemistry. 2012 Dec 21;18(52):16677-88. doi: 10.1002/chem.201202776. Epub 2012, Nov 7. PMID:23135838 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

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