3e4e: Difference between revisions

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-{{Seed}}
-[[Image:3e4e.jpg|left|200px]]
-<!--
+==Human cytochrome P450 2E1 in complex with the inhibitor 4-methylpyrazole==
-The line below this paragraph, containing "STRUCTURE_3e4e", creates the "Structure Box" on the page.
+<StructureSection load='3e4e' size='340' side='right'caption='[[3e4e]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3e4e]] 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=3E4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E4E FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PZ:4-METHYL-1H-PYRAZOLE'>4PZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-{{STRUCTURE_3e4e|  PDB=3e4e  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4e OCA], [https://pdbe.org/3e4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e4e RCSB], [https://www.ebi.ac.uk/pdbsum/3e4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e4e ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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.
+== 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/e4/3e4e_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=3e4e ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates &gt; 70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 angstroms for an indazole complex and 2.6 angstroms for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr303 within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe478 aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved 216QXXNN220 residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed omega-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.
-===Human cytochrome P450 2E1 in complex with the inhibitor 4-methylpyrazole===
+Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates.,Porubsky PR, Meneely KM, Scott EE J Biol Chem. 2008 Nov 28;283(48):33698-707. Epub 2008 Sep 24. PMID:18818195<ref>PMID:18818195</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3e4e" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-E4E 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=3E4E OCA].
+*[[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: Meneely KM]]
-[[Category: Meneely, K M.]]
+[[Category: Porubsky PR]]
-[[Category: Porubsky, P R.]]
+[[Category: Scott EE]]
-[[Category: Scott, E E.]]
-[[Category: Acetaminophen]]
-[[Category: Cyp2e1]]
-[[Category: Endoplasmic reticulum]]
-[[Category: Heme]]
-[[Category: Iron]]
-[[Category: Membrane]]
-[[Category: Metal-binding]]
-[[Category: Microsome]]
-[[Category: Monooxygenase]]
-[[Category: Oxidoreductase]]
-[[Category: P450 2e1]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 17 14:38:09 2008''