6BLD
Mycobacterium marinum cytochrome P450 CYP268A2 in complex with pseudoionone
Summary for 6BLD
| Entry DOI | 10.2210/pdb6bld/pdb |
| Descriptor | Cytochrome P450 268A2 Cyp268A2, PROTOPORPHYRIN IX CONTAINING FE, (3E,5E)-6,10-dimethylundeca-3,5,9-trien-2-one, ... (4 entities in total) |
| Functional Keywords | cytochrome p450, monooxygenase, heme protein, oxidoreductase |
| Biological source | Mycobacterium marinum |
| Total number of polymer chains | 1 |
| Total formula weight | 46865.70 |
| Authors | Child, S.A.,Bruning, J.B.,Bell, S.G. (deposition date: 2017-11-09, release date: 2018-01-24, Last modification date: 2023-10-04) |
| Primary citation | Child, S.A.,Naumann, E.F.,Bruning, J.B.,Bell, S.G. Structural and functional characterisation of the cytochrome P450 enzyme CYP268A2 from Biochem. J., 475:705-722, 2018 Cited by PubMed Abstract: Members of the cytochrome P450 monooxygenase family CYP268 are found across a broad range of species including the pathogens , , , and CYP268A2, from , which is the first member of this family to be studied, was purified and characterised. CYP268A2 was found to bind a variety of substrates with high affinity, including branched and straight chain fatty acids (C10-C12), acetate esters, and aromatic compounds. The enzyme was also found to bind phenylimidazole inhibitors but not larger azoles, such as ketoconazole. The monooxygenase activity of CYP268A2 was efficiently reconstituted using heterologous electron transfer partner proteins. CYP268A2 hydroxylated geranyl acetate and s-pseudoionone at a terminal methyl group to yield (,)-8-hydroxy-3,7-dimethylocta-2,6-dien-1-yl acetate and (,,)-11-hydroxy-6,10-dimethylundeca-3,5,9-trien-2-one, respectively. The X-ray crystal structure of CYP268A2 was solved to a resolution of 2.0 Å with -pseudoionone bound in the active site. The overall structure was similar to that of the related phytanic acid monooxygenase CYP124A1 enzyme from , which shares 41% sequence identity. The active site is predominantly hydrophobic, but includes the Ser99 and Gln209 residues which form hydrogen bonds with the terminal carbonyl group of the pseudoionone. The structure provided an explanation on why CYP268A2 shows a preference for shorter substrates over the longer chain fatty acids which bind to CYP124A1 and the selective nature of the catalysed monooxygenase activity. PubMed: 29343612DOI: 10.1042/BCJ20170946 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.997 Å) |
Structure validation
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