4GQS
Structure of Human Microsomal Cytochrome P450 (CYP) 2C19
Summary for 4GQS
| Entry DOI | 10.2210/pdb4gqs/pdb |
| Related | 1OG2 1OG5 1PQ2 1R9O 2NNI 2NNJ |
| Descriptor | Cytochrome P450 2C19, PROTOPORPHYRIN IX CONTAINING FE, (4-hydroxy-3,5-dimethylphenyl)(2-methyl-1-benzofuran-3-yl)methanone, ... (5 entities in total) |
| Functional Keywords | monooxygenase, drug metabolizing enzyme, oxidoreductase, heme protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Endoplasmic reticulum membrane; Peripheral membrane protein: P33261 |
| Total number of polymer chains | 4 |
| Total formula weight | 222187.50 |
| Authors | Reynald, R.L.,Sansen, S.,Stout, C.D.,Johnson, E.F. (deposition date: 2012-08-23, release date: 2012-11-14, Last modification date: 2023-09-13) |
| Primary citation | Reynald, R.L.,Sansen, S.,Stout, C.D.,Johnson, E.F. Structural Characterization of Human Cytochrome P450 2C19: ACTIVE SITE DIFFERENCES BETWEEN P450s 2C8, 2C9, AND 2C19. J.Biol.Chem., 287:44581-44591, 2012 Cited by PubMed Abstract: To identify the structural features underlying the distinct substrate and inhibitor profiles of P450 2C19 relative to the closely related human enzymes, P450s 2C8 and 2C9, the atomic structure (Protein Data Bank code 4GQS) of cytochrome P450 2C19 complexed with the inhibitor (2-methyl-1-benzofuran-3-yl)-(4-hydroxy-3,5-dimethylphenyl)methanone (Protein Data Bank chemical component 0XV) was determined to 2.87 Å resolution by x-ray crystallography. The conformation of the peptide backbone of P450 2C19 is most similar to that of P450 2C8, but the substrate-binding cavity of P450 2C8 is much larger than that of P450 2C19 due to differences in the amino acid residues that form the substrate-binding cavities of the two enzymes. In contrast, the substrate-binding cavity of P450 2C19 is much more similar in size to that of the structure of the P450 2C9 flurbiprofen complex than to that of a modified P450 2C9 or that of P450 2C8. The cavities of the P450 2C19 0XV complex and the P450 2C9 flurbiprofen complex differ, however, because the helix B-C loops of the two enzymes are dissimilar. These conformational differences reflect the effects of adjacent structural elements that interact with the B-C loops and that differ between the two enzymes. The availability of a structure for 2C19 will facilitate computational approaches for predictions of substrate and inhibitor binding to this enzyme. PubMed: 23118231DOI: 10.1074/jbc.M112.424895 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.87 Å) |
Structure validation
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