4ejg - Revision history

OCA at 10:51, 13 August 2026

2026-08-13T10:51:32Z

← Older revision		Revision as of 10:51, 13 August 2026
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>		[https://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Cytochromes P450 (CYP) from the 2A subfamily are known for their roles in the metabolism of nicotine, the addictive agent in tobacco, and activation of the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Although both the hepatic CYP2A6 and respiratory CYP2A13 enzymes metabolize these compounds, CYP2A13 does so with much higher catalytic efficiency, but the structural basis for this has been unclear. X-ray structures of nicotine complexes with CYP2A13 (2.5 A) and CYP2A6 (2.3 A) yield a structural rationale for the preferential binding of nicotine to CYP2A13. Additional structures of CYP2A13 with NNK reveal either a single NNK molecule in the active site with orientations corresponding to metabolites known to form DNA adducts and initiate lung cancer (2.35 A) or with two molecules of NNK bound (2.1 A): one in the active site and one in a more distal staging site. Finally, in contrast to prior CYP2A structures with enclosed active sites, CYP2A13 conformations were solved that adopt both open and intermediate conformations resulting from an approximately 2.5 A movement of the F to G helices. This channel occurs in the same region where the second, distal NNK molecule is bound, suggesting that the channel may be used for ligand entry and/or exit from the active site. Altogether these structures provide multiple new snapshots of CYP2A13 conformations that assist in understanding the binding and activation of an important human carcinogen, as well as critical comparisons in the binding of nicotine, one of the most widely used and highly addictive drugs in human use.

			Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone binding and access channel in human cytochrome P450 2A6 and 2A13 enzymes.,DeVore NM, Scott EE J Biol Chem. 2012 Aug 3;287(32):26576-85. Epub 2012 Jun 14. PMID:22700965<ref>PMID:22700965</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4ejg" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 15:02, 14 March 2024

2024-03-14T15:02:55Z

← Older revision		Revision as of 15:02, 14 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejg]] is a 8 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejg]] is a 8 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</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]] 2.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</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=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [https://pdbe.org/4ejg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [https://www.ebi.ac.uk/pdbsum/4ejg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejg 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=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [https://pdbe.org/4ejg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [https://www.ebi.ac.uk/pdbsum/4ejg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN]] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>		[https://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Cytochromes P450 (CYP) from the 2A subfamily are known for their roles in the metabolism of nicotine, the addictive agent in tobacco, and activation of the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Although both the hepatic CYP2A6 and respiratory CYP2A13 enzymes metabolize these compounds, CYP2A13 does so with much higher catalytic efficiency, but the structural basis for this has been unclear. X-ray structures of nicotine complexes with CYP2A13 (2.5 A) and CYP2A6 (2.3 A) yield a structural rationale for the preferential binding of nicotine to CYP2A13. Additional structures of CYP2A13 with NNK reveal either a single NNK molecule in the active site with orientations corresponding to metabolites known to form DNA adducts and initiate lung cancer (2.35 A) or with two molecules of NNK bound (2.1 A): one in the active site and one in a more distal staging site. Finally, in contrast to prior CYP2A structures with enclosed active sites, CYP2A13 conformations were solved that adopt both open and intermediate conformations resulting from an approximately 2.5 A movement of the F to G helices. This channel occurs in the same region where the second, distal NNK molecule is bound, suggesting that the channel may be used for ligand entry and/or exit from the active site. Altogether these structures provide multiple new snapshots of CYP2A13 conformations that assist in understanding the binding and activation of an important human carcinogen, as well as critical comparisons in the binding of nicotine, one of the most widely used and highly addictive drugs in human use.

	Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone binding and access channel in human cytochrome P450 2A6 and 2A13 enzymes.,DeVore NM, Scott EE J Biol Chem. 2012 Aug 3;287(32):26576-85. Epub 2012 Jun 14. PMID:22700965<ref>PMID:22700965</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4ejg" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==

OCA at 07:13, 28 September 2022

2022-09-28T07:13:51Z

← Older revision		Revision as of 07:13, 28 September 2022
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	==Human Cytochrome P450 2A13 in complex with Nicotine==		==Human Cytochrome P450 2A13 in complex with Nicotine==
	<StructureSection load='4ejg' size='340' side='right' caption='[[4ejg]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ejg' size='340' side='right'caption='[[4ejg]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejg]] is a 8 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EJG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejg]] is a 8 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2p85\|2p85]], [[3t3s\|3t3s]], [[4ejh\|4ejh]], [[4eji\|4eji]], [[4ejj\|4ejj]]</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=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [https://pdbe.org/4ejg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [https://www.ebi.ac.uk/pdbsum/4ejg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejg ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2A13 ([http://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'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [~~http~~://pdbe.org/4ejg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ejg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN]] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>		[[https://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN]] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4ejg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ejg" 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: ~~Unspecific monooxygenase~~]]		[[Category: Large Structures]]
	[[Category: DeVore~~, N M~~]]		[[Category: DeVore NM]]
	[[Category: Scott~~, E E]]~~		[[Category: Scott EE]]
	~~[[Category: Cyp2a13]]~~
	~~[[Category: Cytochrome p450 2a13]]~~
	~~[[Category: Drug metabolism]]~~
	~~[[Category: Endoplasmic reticulum]]~~
	~~[[Category: Heme protein]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Monooxygenase]]~~
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: P450 2a13]]~~
	~~[[Category: Xenobiotic metabolism~~]]

OCA at 08:05, 15 November 2017

2017-11-15T08:05:07Z

← Older revision		Revision as of 08:05, 15 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4ejg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ejg" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Cytochrome P450\|Cytochrome P450]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:25, 5 August 2016

2016-08-05T20:25:20Z

← Older revision		Revision as of 20:25, 5 August 2016
Line 1:		Line 1:

	==Human Cytochrome P450 2A13 in complex with Nicotine==		==Human Cytochrome P450 2A13 in complex with Nicotine==
	<StructureSection load='4ejg' size='340' side='right' caption='[[4ejg]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ejg' size='340' side='right' caption='[[4ejg]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejg]] is a 8 chain structure with 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejg]] is a 8 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2p85\|2p85]], [[3t3s\|3t3s]], [[4ejh\|4ejh]], [[4eji\|4eji]], [[4ejj\|4ejj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2p85\|2p85]], [[3t3s\|3t3s]], [[4ejh\|4ejh]], [[4eji\|4eji]], [[4ejj\|4ejj]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2A13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2A13 ([http://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'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [http://www.ebi.ac.uk/pdbsum/4ejg PDBsum]</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=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [http://pdbe.org/4ejg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [http://www.ebi.ac.uk/pdbsum/4ejg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4ejg" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Unspecific monooxygenase]]		[[Category: Unspecific monooxygenase]]
	[[Category: DeVore, N M]]		[[Category: DeVore, N M]]

OCA at 21:37, 25 December 2014

2014-12-25T21:37:31Z

← Older revision		Revision as of 21:37, 25 December 2014
Line 9:		Line 9:
	<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=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [http://www.ebi.ac.uk/pdbsum/4ejg PDBsum]</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=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [http://www.ebi.ac.uk/pdbsum/4ejg PDBsum]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN]] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:17, 9 December 2014

2014-12-09T17:17:04Z

← Older revision		Revision as of 17:17, 9 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~4ejg~~.~~png~~\|~~left~~\|~~200px~~]]		==Human Cytochrome P450 2A13 in complex with Nicotine==
			<StructureSection load='4ejg' size='340' side='right' caption='[[4ejg]], [[Resolution\|resolution]] 2.50Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4ejg]] is a 8 chain structure with 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=4EJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJG FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2p85\|2p85]], [[3t3s\|3t3s]], [[4ejh\|4ejh]], [[4eji\|4eji]], [[4ejj\|4ejj]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2A13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ejg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejg RCSB], [http://www.ebi.ac.uk/pdbsum/4ejg PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Cytochromes P450 (CYP) from the 2A subfamily are known for their roles in the metabolism of nicotine, the addictive agent in tobacco, and activation of the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Although both the hepatic CYP2A6 and respiratory CYP2A13 enzymes metabolize these compounds, CYP2A13 does so with much higher catalytic efficiency, but the structural basis for this has been unclear. X-ray structures of nicotine complexes with CYP2A13 (2.5 A) and CYP2A6 (2.3 A) yield a structural rationale for the preferential binding of nicotine to CYP2A13. Additional structures of CYP2A13 with NNK reveal either a single NNK molecule in the active site with orientations corresponding to metabolites known to form DNA adducts and initiate lung cancer (2.35 A) or with two molecules of NNK bound (2.1 A): one in the active site and one in a more distal staging site. Finally, in contrast to prior CYP2A structures with enclosed active sites, CYP2A13 conformations were solved that adopt both open and intermediate conformations resulting from an approximately 2.5 A movement of the F to G helices. This channel occurs in the same region where the second, distal NNK molecule is bound, suggesting that the channel may be used for ligand entry and/or exit from the active site. Altogether these structures provide multiple new snapshots of CYP2A13 conformations that assist in understanding the binding and activation of an important human carcinogen, as well as critical comparisons in the binding of nicotine, one of the most widely used and highly addictive drugs in human use.

	~~{{STRUCTURE_4ejg\| PDB=4ejg \| SCENE= }}~~		Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone binding and access channel in human cytochrome P450 2A6 and 2A13 enzymes.,DeVore NM, Scott EE J Biol Chem. 2012 Aug 3;287(32):26576-85. Epub 2012 Jun 14. PMID:22700965<ref>PMID:22700965</ref>

	~~===Human Cytochrome P450 2A13 in complex with Nicotine===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_22700965}}~~		==See Also==
			*[[Cytochrome P450\|Cytochrome P450]]
	==~~About this Structure~~==		== References ==
	[[~~4ejg~~]] ~~is a 8 chain structure with 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=4EJG OCA].~~		<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Unspecific monooxygenase]]		[[Category: Unspecific monooxygenase]]
	[[Category: DeVore, N M.]]		[[Category: DeVore, N M]]
	[[Category: Scott, E E.]]		[[Category: Scott, E E]]
	[[Category: Cyp2a13]]		[[Category: Cyp2a13]]
	[[Category: Cytochrome p450 2a13]]		[[Category: Cytochrome p450 2a13]]

OCA at 07:13, 2 January 2013

2013-01-02T07:13:16Z

← Older revision		Revision as of 07:13, 2 January 2013
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	{{STRUCTURE_4ejg\| PDB=4ejg \| SCENE= }}		{{STRUCTURE_4ejg\| PDB=4ejg \| SCENE= }}

	===Human Cytochrome P450 2A13 in complex with Nicotine===		===Human Cytochrome P450 2A13 in complex with Nicotine===

			{{ABSTRACT_PUBMED_22700965}}

	==About this Structure==		==About this Structure==

OCA at 07:56, 6 June 2012

2012-06-06T07:56:13Z

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-'''Unreleased structure'''
+[[Image:4ejg.jpg|left|200px]]
-The entry 4ejg is ON HOLD
+<!--
-Authors: DeVore, N.M., Scott, E.E.
+===Human Cytochrome P450 2A13 in complex with Nicotine===
-Description: Human Cytochrome P450 2A13 in complex with Nicotine

OCA: Protected "4ejg" [edit=sysop:move=sysop]

2012-04-18T07:32:41Z

Protected "4ejg" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:32, 18 April 2012
(No difference)