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| | ==Structure of Human Microsomal Cytochrome P450 (CYP) 2C19== | | ==Structure of Human Microsomal Cytochrome P450 (CYP) 2C19== |
| - | <StructureSection load='4gqs' size='340' side='right' caption='[[4gqs]], [[Resolution|resolution]] 2.87Å' scene=''> | + | <StructureSection load='4gqs' size='340' side='right'caption='[[4gqs]], [[Resolution|resolution]] 2.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gqs]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GQS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gqs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GQS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0XV:(4-HYDROXY-3,5-DIMETHYLPHENYL)(2-METHYL-1-BENZOFURAN-3-YL)METHANONE'>0XV</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0XV:(4-HYDROXY-3,5-DIMETHYLPHENYL)(2-METHYL-1-BENZOFURAN-3-YL)METHANONE'>0XV</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1r9o|1r9o]], [[1og2|1og2]], [[1og5|1og5]], [[1pq2|1pq2]], [[2nnj|2nnj]], [[2nni|2nni]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gqs OCA], [https://pdbe.org/4gqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gqs RCSB], [https://www.ebi.ac.uk/pdbsum/4gqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gqs ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2C19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gqs OCA], [http://pdbe.org/4gqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gqs RCSB], [http://www.ebi.ac.uk/pdbsum/4gqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gqs ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CP2CJ_HUMAN CP2CJ_HUMAN]] Resistance to clopidogrel;Antidepressant or antipsychotics toxicity or dose selection;Voriconazole toxicity. | + | [https://www.uniprot.org/uniprot/CP2CJ_HUMAN CP2CJ_HUMAN] Resistance to clopidogrel;Antidepressant or antipsychotics toxicity or dose selection;Voriconazole toxicity. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CP2CJ_HUMAN CP2CJ_HUMAN]] Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. | + | [https://www.uniprot.org/uniprot/CP2CJ_HUMAN CP2CJ_HUMAN] Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Cytochrome P450|Cytochrome P450]] | + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Johnson, E F]] | + | [[Category: Large Structures]] |
| - | [[Category: Reynald, R L]] | + | [[Category: Johnson EF]] |
| - | [[Category: Sansen, S]] | + | [[Category: Reynald RL]] |
| - | [[Category: Stout, C D]] | + | [[Category: Sansen S]] |
| - | [[Category: Drug metabolizing enzyme]] | + | [[Category: Stout CD]] |
| - | [[Category: Heme protein]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
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| Structural highlights
Disease
CP2CJ_HUMAN Resistance to clopidogrel;Antidepressant or antipsychotics toxicity or dose selection;Voriconazole toxicity.
Function
CP2CJ_HUMAN Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Publication Abstract from PubMed
In order to identify 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 (PDB#4GQS) of cytochrome P450 2C19 complexed with the inhibitor (2-methyl-1-benzofuran-3-yl)-(4-hydroxy-3,5-dimethylphenyl)methanone (PDB chemical component: 0XV) was determined to 2.87 A 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 P450 2C9 flurbiprofen complex than to that of a modified P450 2C9 or that of P450 2C8. The cavities of 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 conformation differences reflect 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.
Structural characterization of human cytochrome P450 2C19: active site differences between P450's 2C8, 2C9 and 2C19.,Reynald RL, Sansen S, Stout CD, Johnson EF J Biol Chem. 2012 Nov 1. PMID:23118231[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Reynald RL, Sansen S, Stout CD, Johnson EF. Structural characterization of human cytochrome P450 2C19: active site differences between P450's 2C8, 2C9 and 2C19. J Biol Chem. 2012 Nov 1. PMID:23118231 doi:http://dx.doi.org/10.1074/jbc.M112.424895
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