3ua1 - Revision history

OCA at 13:52, 14 March 2024

OCA — Thu, 14 Mar 2024 13:52:19 GMT

←Older revision		Revision as of 13:52, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3ua1' size='340' side='right'caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3ua1' size='340' side='right'caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>~~, ~~<scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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]] 2.15Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">CYP3A4, CYP3A3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [https://pdbe.org/3ua1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [https://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [https://pdbe.org/3ua1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [https://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</ref>	+	[https://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Cytochrome P4503A4 (CYP3A4), a major human drug-metabolizing enzyme, is responsible for the oxidation and clearance of the majority of administered drugs. One of the CYP3A4 substrates is bromoergocryptine (BEC), a dopamine receptor agonist prescribed for the inhibition of prolactin secretion and treatment of Parkinson disease, type 2 diabetes and several other pathological conditions. Here we present a 2.15 Angstrom crystal structure of the CYP3A4-BEC complex where the drug, a type I heme ligand, is bound in a productive mode. The manner of BEC binding is consistent with the in vivo metabolite analysis and identifies the 8 and 9 carbons of the proline ring as the primary sites of oxidation. The crystal structure predicts the importance of Arg212 and Thr224 for binding of the tripeptide and lysergic moieties of BEC, respectively, which we experimentally confirmed. Our data support a three-step BEC binding model, according to which the drug binds first at a peripheral site without perturbing the heme spectrum and then translocates into the active site cavity, where formation of a hydrogen bond between Thr224 and the N1 atom of the lysergic moiety is followed by a slower conformational readjustment of the tripeptide group modulated by Arg212.	+
-		+
-	Structural and mechanistic insights into the interaction of cytochrome P4503A4 with Bromoergocryptine, a type I ligand.,Sevrioukova IF, Poulos TL J Biol Chem. 2011 Dec 7. PMID:22157006<ref>PMID:22157006</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3ua1" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Poulos~~, T L~~]]	+	[[Category: Poulos TL]]
-	[[Category: Sevrioukova~~, I F]]~~	+	[[Category: Sevrioukova IF]]
-	~~[[Category: Cytochrome b5]]~~	+
-	~~[[Category: Cytochrome p450 reductase]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Protein-substrate complex~~]]	+

OCA at 06:04, 13 July 2022

OCA — Wed, 13 Jul 2022 06:04:27 GMT

←Older revision		Revision as of 06:04, 13 July 2022
Line 1:		Line 1:

	==Crystal structure of the cytochrome P4503A4-bromoergocryptine complex==		==Crystal structure of the cytochrome P4503A4-bromoergocryptine complex==
-	<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>	+	<StructureSection load='3ua1' size='340' side='right'caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A4, CYP3A3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A4, CYP3A3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [~~http~~://pdbe.org/3ua1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [https://pdbe.org/3ua1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [https://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</ref>	+	[[https://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3ua1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ua1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]
	[[Category: Sevrioukova, I F]]		[[Category: Sevrioukova, I F]]

OCA at 10:01, 8 November 2017

OCA — Wed, 08 Nov 2017 10:01:27 GMT

←Older revision		Revision as of 10:01, 8 November 2017
Line 3:		Line 3:
	<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ua1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A4, CYP3A3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://pdbe.org/3ua1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://pdbe.org/3ua1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]
	[[Category: Sevrioukova, I F]]		[[Category: Sevrioukova, I F]]

OCA at 12:20, 6 November 2017

OCA — Mon, 06 Nov 2017 12:20:06 GMT

←Older revision		Revision as of 12:20, 6 November 2017
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 3ua1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ua1" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Cytochrome P450\|Cytochrome P450]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:22, 3 August 2017

OCA — Thu, 03 Aug 2017 11:22:18 GMT

←Older revision		Revision as of 11:22, 3 August 2017
Line 3:		Line 3:
	<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ua1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A4, CYP3A3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://pdbe.org/3ua1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://pdbe.org/3ua1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</span></td></tr>
	</table>		</table>
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]
	[[Category: Sevrioukova, I F]]		[[Category: Sevrioukova, I F]]

OCA at 07:28, 5 August 2016

OCA — Fri, 05 Aug 2016 07:28:49 GMT

←Older revision		Revision as of 07:28, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the cytochrome P4503A4-bromoergocryptine complex==		==Crystal structure of the cytochrome P4503A4-bromoergocryptine complex==
	<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A4, CYP3A3 ([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">CYP3A4, CYP3A3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://pdbe.org/3ua1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ua1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3ua1" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]
	[[Category: Sevrioukova, I F]]		[[Category: Sevrioukova, I F]]

OCA at 00:16, 25 December 2014

OCA — Thu, 25 Dec 2014 00:16:04 GMT

←Older revision		Revision as of 00:16, 25 December 2014
Line 8:		Line 8:
	<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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:24, 9 December 2014

OCA — Tue, 09 Dec 2014 17:24:35 GMT

←Older revision		Revision as of 17:24, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3ua1.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of the cytochrome P4503A4-bromoergocryptine complex==
		+	<StructureSection load='3ua1' size='340' side='right' caption='[[3ua1]], [[Resolution\|resolution]] 2.15Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3ua1]] is a 1 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=3UA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UA1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1tqn\|1tqn]], [[3nxu\|3nxu]], [[2jod\|2jod]], [[2vom\|2vom]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A4, CYP3A3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3ua1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ua1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ua1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ua1 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cytochrome P4503A4 (CYP3A4), a major human drug-metabolizing enzyme, is responsible for the oxidation and clearance of the majority of administered drugs. One of the CYP3A4 substrates is bromoergocryptine (BEC), a dopamine receptor agonist prescribed for the inhibition of prolactin secretion and treatment of Parkinson disease, type 2 diabetes and several other pathological conditions. Here we present a 2.15 Angstrom crystal structure of the CYP3A4-BEC complex where the drug, a type I heme ligand, is bound in a productive mode. The manner of BEC binding is consistent with the in vivo metabolite analysis and identifies the 8 and 9 carbons of the proline ring as the primary sites of oxidation. The crystal structure predicts the importance of Arg212 and Thr224 for binding of the tripeptide and lysergic moieties of BEC, respectively, which we experimentally confirmed. Our data support a three-step BEC binding model, according to which the drug binds first at a peripheral site without perturbing the heme spectrum and then translocates into the active site cavity, where formation of a hydrogen bond between Thr224 and the N1 atom of the lysergic moiety is followed by a slower conformational readjustment of the tripeptide group modulated by Arg212.

-	~~{{STRUCTURE_3ua1\| PDB=3ua1 \| SCENE= }}~~	+	Structural and mechanistic insights into the interaction of cytochrome P4503A4 with Bromoergocryptine, a type I ligand.,Sevrioukova IF, Poulos TL J Biol Chem. 2011 Dec 7. PMID:22157006<ref>PMID:22157006</ref>

-	~~===Crystal structure~~ of the ~~cytochrome P4503A4-bromoergocryptine complex===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_22157006}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3ua1]] is a 1 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=3UA1 OCA].~~	+

	==See Also==		==See Also==
	*[[Cytochrome P450\|Cytochrome P450]]		*[[Cytochrome P450\|Cytochrome P450]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:022157006<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Poulos, T L.]]	+	[[Category: Poulos, T L]]
-	[[Category: Sevrioukova, I F.]]	+	[[Category: Sevrioukova, I F]]
	[[Category: Cytochrome b5]]		[[Category: Cytochrome b5]]
	[[Category: Cytochrome p450 reductase]]		[[Category: Cytochrome p450 reductase]]

OCA at 10:34, 20 October 2012

OCA — Sat, 20 Oct 2012 10:34:37 GMT

←Older revision		Revision as of 10:34, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3ua1]] is a 1 chain structure ~~of [[Cytochrome P450]]~~ 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=3UA1 OCA].	+	[[3ua1]] is a 1 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=3UA1 OCA].

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

OCA at 02:34, 26 July 2012

OCA — Thu, 26 Jul 2012 02:34:59 GMT

←Older revision		Revision as of 02:34, 26 July 2012
Line 1:		Line 1:
	[[Image:3ua1.png\|left\|200px]]		[[Image:3ua1.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_3ua1\| PDB=3ua1 \| SCENE= }}		{{STRUCTURE_3ua1\| PDB=3ua1 \| SCENE= }}

	===Crystal structure of the cytochrome P4503A4-bromoergocryptine complex===		===Crystal structure of the cytochrome P4503A4-bromoergocryptine complex===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22157006}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22157006 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_22157006}}		{{ABSTRACT_PUBMED_22157006}}

	==About this Structure==		==About this Structure==
-	[[3ua1]] is a 1 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=3UA1 OCA].	+	[[3ua1]] is a 1 chain structure of [[Cytochrome P450]] 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=3UA1 OCA].
		+
		+	==See Also==
		+	*[[Cytochrome P450\|Cytochrome P450]]

	==Reference==		==Reference==