3ebs

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:00, 30 August 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3ebs.png|left|200px]]
 
-
<!--
+
==Human Cytochrome P450 2A6 I208S/I300F/G301A/S369G in complex with Phenacetin==
-
The line below this paragraph, containing "STRUCTURE_3ebs", creates the "Structure Box" on the page.
+
<StructureSection load='3ebs' size='340' side='right'caption='[[3ebs]], [[Resolution|resolution]] 2.15&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'>[[3ebs]] 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=3EBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EBS 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]] 2.15&#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=N4E:N-(4-ETHOXYPHENYL)ACETAMIDE'>N4E</scene></td></tr>
-
{{STRUCTURE_3ebs| PDB=3ebs | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ebs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ebs OCA], [https://pdbe.org/3ebs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ebs RCSB], [https://www.ebi.ac.uk/pdbsum/3ebs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ebs ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/CP2A6_HUMAN CP2A6_HUMAN] Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.<ref>PMID:1889415</ref> <ref>PMID:1944238</ref> <ref>PMID:11695850</ref> <ref>PMID:16086027</ref> <ref>PMID:17125252</ref> <ref>PMID:18779312</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/eb/3ebs_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=3ebs ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Cytochrome P450s (P450s) metabolize a large number of diverse substrates with specific regio- and stereospecificity. A number of compounds, including nicotine, cotinine, and aflatoxin B(1), are metabolites of the 94% identical CYP2A13 and CYP2A6 enzymes but at different rates. Phenacetin and 4-aminobiphenyl were identified as substrates of human cytochromes P450 1A2 and 2A13 but not of CYP2A6. The purpose of this study was to identify active site amino acids that are responsible for CYP2A substrate specificity using phenacetin as a structural probe. Ten amino acid residues that differ in the CYP2A13 and CYP2A6 active sites were exchanged between the two enzymes. Phenacetin binding revealed that the six substitution, CYP2A13 S208I, A213S, F300I, A301G, M365V, and G369S decreased phenacetin affinity. Although incorporation of individual CYP2A13 residues into CYP2A6 had little effect on this enzyme's very low levels of phenacetin metabolism, the combination of double, triple, and quadruple substitutions at positions 208, 300, 301, and 369 increasingly endowed CYP2A6 with the ability to metabolize phenacetin. Enzyme kinetics revealed that the CYP2A6 I208S/I300F/G301A/S369G mutant protein O-deethylated phenacetin with a K(m) of 10.3 muM and a k(cat) of 2.9 min(-1), which compare very favorably with those of CYP2A13 (K(m) of 10.7 muM and k(cat) of 3.8 min(-1)). A 2.15 A crystal structure of the mutant CYP2A6 I208S/I300F/G301A/S369G protein with phenacetin in the active site provided a structural rationale for the differences in phenacetin metabolism between CYP2A6 and CYP2A13.
-
===Human Cytochrome P450 2A6 I208S/I300F/G301A/S369G in complex with Phenacetin===
+
Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes.,DeVore NM, Smith BD, Urban MJ, Scott EE Drug Metab Dispos. 2008 Dec;36(12):2582-90. Epub 2008 Sep 8. PMID:18779312<ref>PMID:18779312</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3ebs" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_18779312}}, adds the Publication Abstract to the page
+
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 18779312 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_18779312}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
3EBS is a 4 chains structure of sequences 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=3EBS OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:18779312</ref><references group="xtra"/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Unspecific monooxygenase]]
+
[[Category: Large Structures]]
-
[[Category: DeVore, N M.]]
+
[[Category: DeVore NM]]
-
[[Category: Scott, E E.]]
+
[[Category: Scott EE]]
-
[[Category: Cyp2a13]]
+
-
[[Category: Cyp2a6]]
+
-
[[Category: Endoplasmic reticulum]]
+
-
[[Category: Heme]]
+
-
[[Category: Iron]]
+
-
[[Category: Membrane]]
+
-
[[Category: Metal-binding]]
+
-
[[Category: Microsome]]
+
-
[[Category: Monooxygenase]]
+
-
[[Category: Oxidoreducatase]]
+
-
[[Category: Oxidoreductase]]
+
-
[[Category: P450 2a13]]
+
-
[[Category: P450 2a6]]
+
-
[[Category: Phenacetin]]
+
-
[[Category: Polymorphism]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 05:44:31 2009''
+

Current revision

Human Cytochrome P450 2A6 I208S/I300F/G301A/S369G in complex with Phenacetin

PDB ID 3ebs

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ebs"
Personal tools