3PM0
Structural Characterization of the Complex between Alpha-Naphthoflavone and Human Cytochrome P450 1B1 (CYP1B1)
Summary for 3PM0
| Entry DOI | 10.2210/pdb3pm0/pdb |
| Related | 2HI4 |
| Descriptor | Cytochrome P450 1B1, PROTOPORPHYRIN IX CONTAINING FE, 2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE, ... (4 entities in total) |
| Functional Keywords | cyp1b1, p450 1b1, p450, monooxygenase, alpha-naphthoflavone, heme, 17beta-estradiol, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Cellular location | Endoplasmic reticulum membrane; Peripheral membrane protein: Q16678 |
| Total number of polymer chains | 1 |
| Total formula weight | 57792.73 |
| Authors | Wang, A.,Stout, C.D.,Johnson, E.F. (deposition date: 2010-11-15, release date: 2010-12-08, Last modification date: 2024-02-21) |
| Primary citation | Wang, A.,Savas, U.,Stout, C.D.,Johnson, E.F. Structural Characterization of the Complex between {alpha}-Naphthoflavone and Human Cytochrome P450 1B1. J.Biol.Chem., 286:5736-5743, 2011 Cited by PubMed Abstract: The atomic structure of human P450 1B1 was determined by x-ray crystallography to 2.7 Å resolution with α-naphthoflavone (ANF) bound in the active site cavity. Although the amino acid sequences of human P450s 1B1 and 1A2 have diverged significantly, both enzymes exhibit narrow active site cavities, which underlie similarities in their substrate profiles. Helix I residues adopt a relatively flat conformation in both enzymes, and a characteristic distortion of helix F places Phe(231) in 1B1 and Phe(226) in 1A2 in similar positions for π-π stacking with ANF. ANF binds in a distinctly different orientation in P450 1B1 from that observed for 1A2. This reflects, in part, divergent conformations of the helix B'-C loop that are stabilized by different hydrogen-bonding interactions in the two enzymes. Additionally, differences between the two enzymes for other amino acids that line the edges of the cavity contribute to distinct orientations of ANF in the two active sites. Thus, the narrow cavity is conserved in both P450 subfamily 1A and P450 subfamily 1B with sequence divergence around the edges of the cavity that modify substrate and inhibitor binding. The conservation of these P450 1B1 active site amino acid residues across vertebrate species suggests that these structural features are conserved. PubMed: 21147782DOI: 10.1074/jbc.M110.204420 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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