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| | ==Human Cytochrome P450 2E1 in complex with pilocarpine== | | ==Human Cytochrome P450 2E1 in complex with pilocarpine== |
| - | <StructureSection load='3t3z' size='340' side='right' caption='[[3t3z]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='3t3z' size='340' side='right'caption='[[3t3z]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3t3z]] 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=3T3Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T3Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3t3z]] 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=3T3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T3Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9PL:(3S,4R)-3-ETHYL-4-[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]DIHYDROFURAN-2(3H)-ONE'>9PL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3e4e|3e4e]], [[3e6i|3e6i]], [[3lc4|3lc4]], [[3koh|3koh]], [[3gph|3gph]], [[3t3q|3t3q]], [[3t3s|3t3s]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9PL:(3S,4R)-3-ETHYL-4-[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]DIHYDROFURAN-2(3H)-ONE'>9PL</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2E, CYP2E1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3t3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3z OCA], [https://pdbe.org/3t3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t3z RCSB], [https://www.ebi.ac.uk/pdbsum/3t3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t3z ProSAT]</span></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=3t3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3z OCA], [http://pdbe.org/3t3z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t3z RCSB], [http://www.ebi.ac.uk/pdbsum/3t3z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t3z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CP2E1_HUMAN CP2E1_HUMAN]] Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms. | + | [https://www.uniprot.org/uniprot/CP2E1_HUMAN CP2E1_HUMAN] Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3t3z" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3t3z" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: DeVore, N M]] | + | [[Category: Large Structures]] |
| - | [[Category: Meneely, K M]] | + | [[Category: DeVore NM]] |
| - | [[Category: Scott, E E]] | + | [[Category: Meneely KM]] |
| - | [[Category: Cyp2e1]] | + | [[Category: Scott EE]] |
| - | [[Category: Cytochrome p450 2e1]]
| + | |
| - | [[Category: Drug metabolism]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Heme protein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: P450 2e1]]
| + | |
| - | [[Category: Xenobiotic metabolism]]
| + | |
| Structural highlights
3t3z is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.35Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CP2E1_HUMAN Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Publication Abstract from PubMed
Human xenobiotic-metabolizing cytochrome P450 (CYP) enzymes can each bind and monooxygenate a diverse set of substrates, including drugs, often producing a variety of metabolites. Additionally, a single ligand can interact with multiple CYP enzymes, but often the protein structural similarities and differences that mediate such overlapping selectivity are not well understood. Even though the CYP superfamily has a highly canonical global protein fold, there are large variations in the active site size, topology, and conformational flexibility. We have determined how a related set of three human CYP enzymes bind and interact with a common inhibitor, the muscarinic receptor agonist drug pilocarpine. Pilocarpine binds and inhibits the hepatic CYP2A6 and respiratory CYP2A13 enzymes much more efficiently than the hepatic CYP2E1 enzyme. To elucidate key residues involved in pilocarpine binding, crystal structures of CYP2A6 (2.4 A), CYP2A13 (3.0 A), CYP2E1 (2.35 A), and the CYP2A6 mutant enzyme, CYP2A6 I208S/I300F/G301A/S369G (2.1 A) have been determined with pilocarpine in the active site. In all four structures, pilocarpine coordinates to the heme iron, but comparisons reveal how individual residues lining the active sites of these three distinct human enzymes interact differently with the inhibitor pilocarpine. Database Structural data are available in the Protein Data Bank database under the accession numbers 3T3Q (CYP2A6 I208S/I300F/G301A/S369G with pilocarpine), 3T3R (CYP2A6 with pilocarpine), 3T3S (CYP2A13 with pilocarpine), and 3T3Z (CYP2E1 with pilocarpine).
Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine.,Devore NM, Meneely KM, Bart AG, Stephens ES, Battaile KP, Scott EE FEBS J. 2011 Nov 3. doi: 10.1111/j.1742-4658.2011.08412.x. PMID:22051186[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Devore NM, Meneely KM, Bart AG, Stephens ES, Battaile KP, Scott EE. Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine. FEBS J. 2011 Nov 3. doi: 10.1111/j.1742-4658.2011.08412.x. PMID:22051186 doi:10.1111/j.1742-4658.2011.08412.x
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