4k9t - Revision history

OCA at 15:55, 20 September 2023

OCA — Wed, 20 Sep 2023 15:55:51 GMT

←Older revision		Revision as of 15:55, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4k9t]] 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=4K9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K9T FirstGlance]. <br>		<table><tr><td colspan='2'>[[4k9t]] 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=4K9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K9T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [https://pdbe.org/4k9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [https://www.ebi.ac.uk/pdbsum/4k9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9t 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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [https://pdbe.org/4k9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [https://www.ebi.ac.uk/pdbsum/4k9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9t ProSAT]</span></td></tr>
	</table>		</table>

OCA at 11:47, 30 November 2022

OCA — Wed, 30 Nov 2022 11:47:59 GMT

←Older revision		Revision as of 11:47, 30 November 2022
Line 1:		Line 1:

	==Complex of CYP3A4 with a desoxyritonavir analog==		==Complex of CYP3A4 with a desoxyritonavir analog==
-	<StructureSection load='4k9t' size='340' side='right' caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='4k9t' size='340' side='right'caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4k9t]] 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=4K9T OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4K9T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4k9t]] 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=4K9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K9T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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">[[3nxu\|3nxu]], [[4i4g\|4i4g]], [[4i4h\|4i4h]], [[4k9u\|4k9u]], [[4k9v\|4k9v]], [[4k9w\|4k9w]], [[4k9x\|4k9x]]</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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [https://pdbe.org/4k9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [https://www.ebi.ac.uk/pdbsum/4k9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9t ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A3, CYP3A4 ([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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [~~http~~://pdbe.org/4k9t PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4k9t PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9t 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 18:
	</div>		</div>
	<div class="pdbe-citations 4k9t" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4k9t" 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: ~~Poulos, T L~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Sevrioukova, I F~~]]	+	[[Category: Poulos TL]]
-	[[Category: ~~Alpha-beta protein]]~~	+	[[Category: Sevrioukova IF]]
-	~~[[Category: Cytochrome p450 3a4]]~~	+
-	~~[[Category: Cytochrome p450 fold]]~~	+
-	~~[[Category: Cytochrome p450 reductase]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 09:45, 25 October 2017

OCA — Wed, 25 Oct 2017 09:45:18 GMT

←Older revision		Revision as of 09:45, 25 October 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4k9t" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4k9t" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Cytochrome P450\|Cytochrome P450]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:30, 4 August 2016

OCA — Thu, 04 Aug 2016 08:30:44 GMT

←Older revision		Revision as of 08:30, 4 August 2016
Line 1:		Line 1:
		+
	==Complex of CYP3A4 with a desoxyritonavir analog==		==Complex of CYP3A4 with a desoxyritonavir analog==
	<StructureSection load='4k9t' size='340' side='right' caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4k9t' size='340' side='right' caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nxu\|3nxu]], [[4i4g\|4i4g]], [[4i4h\|4i4h]], [[4k9u\|4k9u]], [[4k9v\|4k9v]], [[4k9w\|4k9w]], [[4k9x\|4k9x]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nxu\|3nxu]], [[4i4g\|4i4g]], [[4i4h\|4i4h]], [[4k9u\|4k9u]], [[4k9v\|4k9v]], [[4k9w\|4k9w]], [[4k9x\|4k9x]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A3, CYP3A4 ([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">CYP3A3, CYP3A4 ([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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [http://www.ebi.ac.uk/pdbsum/4k9t 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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [http://pdbe.org/4k9t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [http://www.ebi.ac.uk/pdbsum/4k9t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9t 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 4k9t" style="background-color:#fffaf0;"></div>

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

OCA at 07:21, 25 December 2014

OCA — Thu, 25 Dec 2014 07:21:37 GMT

←Older revision		Revision as of 07:21, 25 December 2014
Line 2:		Line 2:
	<StructureSection load='4k9t' size='340' side='right' caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4k9t' size='340' side='right' caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4k9t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K9T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K9T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4k9t]] 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=4K9T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K9T FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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">[[3nxu\|3nxu]], [[4i4g\|4i4g]], [[4i4h\|4i4h]], [[4k9u\|4k9u]], [[4k9v\|4k9v]], [[4k9w\|4k9w]], [[4k9x\|4k9x]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nxu\|3nxu]], [[4i4g\|4i4g]], [[4i4h\|4i4h]], [[4k9u\|4k9u]], [[4k9v\|4k9v]], [[4k9w\|4k9w]], [[4k9x\|4k9x]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP3A3, CYP3A4 ([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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [http://www.ebi.ac.uk/pdbsum/4k9t 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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [http://www.ebi.ac.uk/pdbsum/4k9t 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 15:		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>
		+
		+	==See Also==
		+	*[[Cytochrome P450\|Cytochrome P450]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Poulos, T L.]]	+	[[Category: Human]]
-	[[Category: Sevrioukova, I F.]]	+	[[Category: Poulos, T L]]
		+	[[Category: Sevrioukova, I F]]
	[[Category: Alpha-beta protein]]		[[Category: Alpha-beta protein]]
	[[Category: Cytochrome p450 3a4]]		[[Category: Cytochrome p450 3a4]]

OCA at 09:04, 29 October 2014

OCA — Wed, 29 Oct 2014 09:04:10 GMT

←Older revision		Revision as of 09:04, 29 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4k9t\| PDB=4k9t \| SCENE= }}~~	+	==Complex of CYP3A4 with a desoxyritonavir analog==
-	===Complex of CYP3A4 with a desoxyritonavir analog===	+	<StructureSection load='4k9t' size='340' side='right' caption='[[4k9t]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	{{~~ABSTRACT_PUBMED_23746300}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4k9t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K9T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K9T FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1RD:N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}CARBAMOYL)-N-(4-{[(1,3-THIAZOL-5-YLMETHOXY)CARBONYL]AMINO}BUTYL)-L-VALINAMIDE'>1RD</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">[[3nxu\|3nxu]], [[4i4g\|4i4g]], [[4i4h\|4i4h]], [[4k9u\|4k9u]], [[4k9v\|4k9v]], [[4k9w\|4k9w]], [[4k9x\|4k9x]]</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=4k9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k9t RCSB], [http://www.ebi.ac.uk/pdbsum/4k9t PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cytochrome P450 3A4 (CYP3A4) inhibitors ritonavir and cobicistat, currently administered to HIV patients as pharmacoenhancers, were designed on the basis of the chemical structure/activity relationships rather than the CYP3A4 crystal structure. To better understand the structural basis for CYP3A4 inhibition and the ligand binding process, we investigated five desoxyritonavir analogues to elucidate how substitution/elimination of the phenyl side groups (Phe-1 and Phe-2) and removal of the isopropyl-thiazole (IPT) moiety affect affinity, inhibitory potency, and the ligand binding mode. Our experimental and structural data indicate that the side group size reduction not only drastically lowers affinity and inhibitory potency for CYP3A4 but also leads to multiple binding modes. Regardless of the side group chemical nature and the number of molecules bound, the space adjacent to the 369-371 peptide and Arg105 (Phe-2 site) is always occupied and, hence, must be a critically important binding site. When possible, the ligands also try to fill the pocket near the I-helix (Phe-1 site), even if it causes steric hindrance. Extensive hydrophobic interactions established at the Phe-1 site improve inhibitory potency, whereas contacts provided by IPT might strengthen the Fe-N bond. Overall, however, the end group contributes less to the ligand association process, which, in contrast, is greatly facilitated by the polar interactions mediated by the active site Ser119.

-	~~==Function==~~	+	Dissecting Cytochrome P450 3A4-Ligand Interactions Using Ritonavir Analogues.,Sevrioukova IF, Poulos TL Biochemistry. 2013 Jun 20. PMID:23746300<ref>PMID:23746300</ref>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4k9t]] 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=4K9T OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:023746300</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
-	~~[[Category: Homo sapiens]]~~	+	</StructureSection>
-	[[Category: Poulos, T L..]]	+	[[Category: Poulos, T L.]]
	[[Category: Sevrioukova, I F.]]		[[Category: Sevrioukova, I F.]]
	[[Category: Alpha-beta protein]]		[[Category: Alpha-beta protein]]

OCA at 07:08, 30 June 2013

OCA — Sun, 30 Jun 2013 07:08:49 GMT

←Older revision		Revision as of 07:08, 30 June 2013
Line 1:		Line 1:
	{{STRUCTURE_4k9t\| PDB=4k9t \| SCENE= }}		{{STRUCTURE_4k9t\| PDB=4k9t \| SCENE= }}
	===Complex of CYP3A4 with a desoxyritonavir analog===		===Complex of CYP3A4 with a desoxyritonavir analog===
		+	{{ABSTRACT_PUBMED_23746300}}

	==Function==		==Function==
Line 9:		Line 10:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023746300</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Poulos, T L..]]		[[Category: Poulos, T L..]]

OCA at 07:27, 20 June 2013

OCA — Thu, 20 Jun 2013 07:27:01 GMT

←Older revision		Revision as of 07:27, 20 June 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4k9t\| PDB=4k9t \| SCENE= }}
		+	===Complex of CYP3A4 with a desoxyritonavir analog===

-	~~The entry 4k9t~~ is ~~ON HOLD~~	+	==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>

-	~~Authors~~: ~~Sevrioukova, I~~.F.~~, Poulos, T~~.L..	+	==About this Structure==
		+	[[4k9t]] 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=4K9T OCA].

-	~~Description~~: ~~Complex of CYP3A4 with a desoxyritonavir analog~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Poulos, T L..]]
		+	[[Category: Sevrioukova, I F.]]
		+	[[Category: Alpha-beta protein]]
		+	[[Category: Cytochrome p450 3a4]]
		+	[[Category: Cytochrome p450 fold]]
		+	[[Category: Cytochrome p450 reductase]]
		+	[[Category: Endoplasmic reticulum]]
		+	[[Category: Monooxygenase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 06:53, 16 May 2013

OCA — Thu, 16 May 2013 06:53:58 GMT

←Older revision		Revision as of 06:53, 16 May 2013
Line 3:		Line 3:
	The entry 4k9t is ON HOLD		The entry 4k9t is ON HOLD

-	Authors: Sevrioukova, I. F., Poulos, T. L..	+	Authors: Sevrioukova, I.F., Poulos, T.L..

	Description: Complex of CYP3A4 with a desoxyritonavir analog		Description: Complex of CYP3A4 with a desoxyritonavir analog

OCA: Protected "4k9t" [edit=sysop:move=sysop]

OCA — Thu, 02 May 2013 07:13:30 GMT

Protected "4k9t" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:13, 2 May 2013