4ny4 - Revision history

OCA at 12:36, 1 March 2024

OCA — Fri, 01 Mar 2024 12:36:26 GMT

←Older revision		Revision as of 12:36, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ny4]] 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=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ny4]] 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=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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]] 2.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [https://pdbe.org/4ny4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [https://pdbe.org/4ny4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 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 P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects.
-
-	Structure-based ligand design to overcome CYP inhibition in drug discovery projects.,Branden G, Sjogren T, Schnecke V, Xue Y Drug Discov Today. 2014 Jul;19(7):905-911. doi: 10.1016/j.drudis.2014.03.012., Epub 2014 Mar 16. PMID:24642031<ref>PMID:24642031</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4ny4" style="background-color:#fffaf0;"></div>

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

OCA at 08:45, 18 January 2023

OCA — Wed, 18 Jan 2023 08:45:18 GMT

←Older revision		Revision as of 08:45, 18 January 2023
Line 3:		Line 3:
	<StructureSection load='4ny4' size='340' side='right'caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>		<StructureSection load='4ny4' size='340' side='right'caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ny4]] 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=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ny4]] 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=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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">[[4nz2\|4nz2]]</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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [https://pdbe.org/4ny4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A3, CYP3A4, 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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [~~http~~://pdbe.org/4ny4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 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 23:		Line 21:
	==See Also==		==See Also==
	*[[CYP3A4\|CYP3A4]]		*[[CYP3A4\|CYP3A4]]
-	*[[Cytochrome P450\|Cytochrome P450]]	+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Branden, G]]	+	[[Category: Branden G]]
-	[[Category: Sjogren, T]]	+	[[Category: Sjogren T]]
-	[[Category: Xue, Y]]	+	[[Category: Xue Y]]
-	~~[[Category: Cyp3a4]]~~	+
-	~~[[Category: Cytochrome p-450]]~~	+
-	~~[[Category: Drug metabolism]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Structure-based drug design~~]]	+

OCA at 08:09, 10 April 2019

OCA — Wed, 10 Apr 2019 08:09:24 GMT

←Older revision		Revision as of 08:09, 10 April 2019
Line 1:		Line 1:

	==Crystal structure of CYP3A4 in complex with an inhibitor==		==Crystal structure of CYP3A4 in complex with an inhibitor==
-	<StructureSection load='4ny4' size='340' side='right' caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>	+	<StructureSection load='4ny4' size='340' side='right'caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ny4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ny4]] 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=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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">[[4nz2\|4nz2]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nz2\|4nz2]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A3, CYP3A4, 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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://pdbe.org/4ny4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://pdbe.org/4ny4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:

	==See Also==		==See Also==
		+	*[[CYP3A4\|CYP3A4]]
	*[[Cytochrome P450\|Cytochrome P450]]		*[[Cytochrome P450\|Cytochrome P450]]
	== References ==		== References ==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Branden, G]]		[[Category: Branden, G]]
	[[Category: Sjogren, T]]		[[Category: Sjogren, T]]

OCA at 16:54, 5 August 2016

OCA — Fri, 05 Aug 2016 16:54:16 GMT

←Older revision		Revision as of 16:54, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of CYP3A4 in complex with an inhibitor==		==Crystal structure of CYP3A4 in complex with an inhibitor==
	<StructureSection load='4ny4' size='340' side='right' caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>		<StructureSection load='4ny4' size='340' side='right' caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</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">[[4nz2\|4nz2]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nz2\|4nz2]]</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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://pdbe.org/4ny4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ny4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4ny4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cytochrome P450\|Cytochrome P450]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:27, 25 December 2014

OCA — Thu, 25 Dec 2014 20:27:30 GMT

←Older revision		Revision as of 20:27, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ny4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ny4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nz2\|4nz2]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nz2\|4nz2]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 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=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 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 ==
Line 19:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Branden, G.]]	+	[[Category: Branden, G]]
-	[[Category: Sjogren, T.]]	+	[[Category: Sjogren, T]]
-	[[Category: Xue, Y.]]	+	[[Category: Xue, Y]]
	[[Category: Cyp3a4]]		[[Category: Cyp3a4]]
	[[Category: Cytochrome p-450]]		[[Category: Cytochrome p-450]]

OCA at 08:58, 13 August 2014

OCA — Wed, 13 Aug 2014 08:58:46 GMT

←Older revision		Revision as of 08:58, 13 August 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of CYP3A4 in complex with an inhibitor==
		+	<StructureSection load='4ny4' size='340' side='right' caption='[[4ny4]], [[Resolution\|resolution]] 2.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ny4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NY4 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QH:(8R)-3,3-DIFLUORO-8-[4-FLUORO-3-(PYRIDIN-3-YL)PHENYL]-8-(4-METHOXY-3-METHYLPHENYL)-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>2QH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nz2\|4nz2]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ny4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ny4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ny4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ny4 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cytochrome P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects.

-	~~The entry 4ny4 is ON HOLD~~	+	Structure-based ligand design to overcome CYP inhibition in drug discovery projects.,Branden G, Sjogren T, Schnecke V, Xue Y Drug Discov Today. 2014 Jul;19(7):905-911. doi: 10.1016/j.drudis.2014.03.012., Epub 2014 Mar 16. PMID:24642031<ref>PMID:24642031</ref>

-	~~Authors~~: Branden, G., Sjogren, T., Xue, Y.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of CYP3A4 in complex with an~~ inhibitor	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Branden, G.]]
		+	[[Category: Sjogren, T.]]
		+	[[Category: Xue, Y.]]
		+	[[Category: Cyp3a4]]
		+	[[Category: Cytochrome p-450]]
		+	[[Category: Drug metabolism]]
		+	[[Category: Inhibitor]]
		+	[[Category: Monooxygenase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Structure-based drug design]]

OCA: Protected "4ny4" [edit=sysop:move=sysop]

OCA — Wed, 18 Dec 2013 09:26:50 GMT

Protected "4ny4" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:26, 18 December 2013

OCA: New page: '''Unreleased structure''' The entry 4ny4 is ON HOLD Authors: Branden, G., Sjogren, T., Xue, Y. Description: Crystal structure of CYP3A4 in complex with an inhibitor

OCA — Wed, 18 Dec 2013 09:26:49 GMT

New page: '''Unreleased structure''' The entry 4ny4 is ON HOLD Authors: Branden, G., Sjogren, T., Xue, Y. Description: Crystal structure of CYP3A4 in complex with an inhibitor

New page

'''Unreleased structure'''

The entry 4ny4 is ON HOLD

Authors: Branden, G., Sjogren, T., Xue, Y.

Description: Crystal structure of CYP3A4 in complex with an inhibitor