|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3qm4' size='340' side='right'caption='[[3qm4]], [[Resolution|resolution]] 2.85Å' scene=''> | | <StructureSection load='3qm4' size='340' side='right'caption='[[3qm4]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qm4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QM4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qm4]] is a 2 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=3QM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QM4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PN0:PRINOMASTAT'>PN0</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]] 2.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2f9q|2f9q]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PN0:PRINOMASTAT'>PN0</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2D6, CYP2DL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></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=3qm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qm4 OCA], [https://pdbe.org/3qm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qm4 RCSB], [https://www.ebi.ac.uk/pdbsum/3qm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qm4 ProSAT]</span></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=3qm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qm4 OCA], [https://pdbe.org/3qm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qm4 RCSB], [https://www.ebi.ac.uk/pdbsum/3qm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qm4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CP2D6_HUMAN CP2D6_HUMAN]] Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.<ref>PMID:16352597</ref>
| + | [https://www.uniprot.org/uniprot/CP2D6_HUMAN CP2D6_HUMAN] Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.<ref>PMID:16352597</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Human cytochrome P450 2D6 contributes to the metabolism of >15% of drugs used in clinical practice. This study determined the structure of P450 2D6 complexed with a substrate and potent inhibitor prinomastat to 2.85 A resolution by X-ray crystallography. Prinomastat binding is well defined by electron density maps with its pyridyl nitrogen bound to the heme iron. The structure of ligand bound P450 2D6 differs significantly from the ligand free structure reported for the P450 2D6 Met374 variant (PDB# 2F9Q). Superposition of the structures reveals significant differences for beta sheet 1, helices A, F, F', G", G and H as well as the helix B-C loop. The structure of the ligand complex exhibits a closed active site cavity that conforms closely to the shape of prinomastat. The closure of the open cavity seen for the 2F9Q structure reflects a change in the direction and pitch of helix F and introduction of a turn at Gly-218, which is followed by a well defined helix F' that was not observed in the 2F9Q structure. These differences reflect considerable, structural flexibility that is likely to contribute to the catalytic versatility of P450 2D6 and the new structure provides an alternative model for in silico studies of substrate interactions with P450 2D6.
| + | |
| - | | + | |
| - | Crystal structure of human cytochrome P450 2D6 with prinomastat bound.,Wang A, Savas U, Hsu MH, Stout CD, Johnson EF J Biol Chem. 2012 Feb 3. PMID:22308038<ref>PMID:22308038</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3qm4" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| Line 28: |
Line 17: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Unspecific monooxygenase]]
| + | [[Category: Johnson EF]] |
| - | [[Category: Johnson, E F]] | + | [[Category: Stout CD]] |
| - | [[Category: Stout, C D]] | + | [[Category: Wang A]] |
| - | [[Category: Wang, A]] | + | |
| - | [[Category: Cyp2d6]]
| + | |
| - | [[Category: Heme]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: P450]]
| + | |
| - | [[Category: P450 2d6]]
| + | |
| - | [[Category: Prinomastat]]
| + | |
