1pq2: Difference between revisions

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-[[Image:1pq2.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1pq2", creates the "Structure Box" on the page.
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-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-{{STRUCTURE_1pq2|  PDB=1pq2  |  SCENE=  }}
-'''Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8'''
+==Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8==
+<StructureSection load='1pq2' size='340' side='right'caption='[[1pq2]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1pq2]] 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=1PQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PQ2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</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=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=1pq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pq2 OCA], [https://pdbe.org/1pq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pq2 RCSB], [https://www.ebi.ac.uk/pdbsum/1pq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pq2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CP2C8_HUMAN CP2C8_HUMAN] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).<ref>PMID:7574697</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pq/1pq2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pq2 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A 2.7-Angstrom molecular structure of human microsomal cytochrome P450 2C8 (CYP2C8) was determined by x-ray crystallography. The membrane protein was modified for crystallization by replacement of the hydrophobic N-terminal transmembrane domain with a short hydrophilic sequence before residue 28. The structure of the native sequence is complete from residue 28 to the beginning of a C-terminal histidine tag used for purification. CYP2C8 is one of the principal hepatic drug-metabolizing enzymes that oxidizes therapeutic drugs such as taxol and cerivastatin and endobiotics such as retinoic acid and arachidonic acid. Consistent with the relatively large size of its preferred substrates, the active site volume is twice that observed for the structure of CYP2C5. The extended active site cavity is bounded by the beta1 sheet and helix F' that have not previously been implicated in substrate recognition by mammalian P450s. CYP2C8 crystallized as a symmetric dimer formed by the interaction of helices F, F', G', and G. Two molecules of palmitic acid are bound in the dimer interface. The dimer is observed in solution, and mass spectrometry confirmed the association of palmitic acid with the enzyme. This novel finding identifies a peripheral binding site in P450s that may contribute to drug-drug interactions in P450 metabolism.
-==Overview==
+Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site.,Schoch GA, Yano JK, Wester MR, Griffin KJ, Stout CD, Johnson EF J Biol Chem. 2004 Mar 5;279(10):9497-503. Epub 2003 Dec 15. PMID:14676196<ref>PMID:14676196</ref>
-A 2.7-Angstrom molecular structure of human microsomal cytochrome P450 2C8 (CYP2C8) was determined by x-ray crystallography. The membrane protein was modified for crystallization by replacement of the hydrophobic N-terminal transmembrane domain with a short hydrophilic sequence before residue 28. The structure of the native sequence is complete from residue 28 to the beginning of a C-terminal histidine tag used for purification. CYP2C8 is one of the principal hepatic drug-metabolizing enzymes that oxidizes therapeutic drugs such as taxol and cerivastatin and endobiotics such as retinoic acid and arachidonic acid. Consistent with the relatively large size of its preferred substrates, the active site volume is twice that observed for the structure of CYP2C5. The extended active site cavity is bounded by the beta1 sheet and helix F' that have not previously been implicated in substrate recognition by mammalian P450s. CYP2C8 crystallized as a symmetric dimer formed by the interaction of helices F, F', G', and G. Two molecules of palmitic acid are bound in the dimer interface. The dimer is observed in solution, and mass spectrometry confirmed the association of palmitic acid with the enzyme. This novel finding identifies a peripheral binding site in P450s that may contribute to drug-drug interactions in P450 metabolism.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-PQ2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PQ2 OCA].
+</div>
+<div class="pdbe-citations 1pq2" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site., Schoch GA, Yano JK, Wester MR, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2004 Mar 5;279(10):9497-503. Epub 2003 Dec 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14676196 14676196]
+*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Unspecific monooxygenase]]
+[[Category: Griffin KJ]]
-[[Category: Griffin, K J.]]
+[[Category: Johnson EF]]
-[[Category: Johnson, E F.]]
+[[Category: Schoch GA]]
-[[Category: Schoch, G A.]]
+[[Category: Stout CD]]
-[[Category: Stout, C D.]]
+[[Category: Wester MR]]
-[[Category: Wester, M R.]]
+[[Category: Yano JK]]
-[[Category: Yano, J K.]]
-[[Category: Cyp2c8]]
-[[Category: Cytochrome p450]]
-[[Category: Membrane protein]]
-[[Category: Taxol 6-hydroxylase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:21:20 2008''