6une - Revision history

OCA at 07:55, 11 October 2023

2023-10-11T07:55:03Z

←Older revision		Revision as of 07:55, 11 October 2023
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	<StructureSection load='6une' size='340' side='right'caption='[[6une]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='6une' size='340' side='right'caption='[[6une]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6une]] 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=6UNE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6UNE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6une]] 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=6UNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UNE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QES:tert-butyl+[(2R)-1-(1H-indol-3-yl)-3-{[(2S)-3-oxo-2-(phenylamino)-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}propan-2-yl]carbamate'>QES</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]] 2.55Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QES:tert-butyl+[(2R)-1-(1H-indol-3-yl)-3-{[(2S)-3-oxo-2-(phenylamino)-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}propan-2-yl]carbamate'>QES</scene></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=6une FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6une OCA], [~~http~~://pdbe.org/6une PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6une RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6une PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6une 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=6une FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6une OCA], [https://pdbe.org/6une PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6une RCSB], [https://www.ebi.ac.uk/pdbsum/6une PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6une 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 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6une" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6une" 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: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sevrioukova~~, I F]]~~	+	[[Category: Sevrioukova IF]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Cyp3a4]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 10:34, 26 February 2020

2020-02-26T10:34:35Z

←Older revision		Revision as of 10:34, 26 February 2020
Line 3:		Line 3:
	<StructureSection load='6une' size='340' side='right'caption='[[6une]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='6une' size='340' side='right'caption='[[6une]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6une]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UNE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6une]] 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=6UNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UNE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QES:tert-butyl+[(2R)-1-(1H-indol-3-yl)-3-{[(2S)-3-oxo-2-(phenylamino)-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}propan-2-yl]carbamate'>QES</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QES:tert-butyl+[(2R)-1-(1H-indol-3-yl)-3-{[(2S)-3-oxo-2-(phenylamino)-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}propan-2-yl]carbamate'>QES</scene></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=6une FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6une OCA], [http://pdbe.org/6une PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6une RCSB], [http://www.ebi.ac.uk/pdbsum/6une PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6une 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=6une FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6une OCA], [http://pdbe.org/6une PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6une RCSB], [http://www.ebi.ac.uk/pdbsum/6une PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6une 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>		[[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;">
		+	== Publication Abstract from PubMed ==
		+	Identification of structural determinants required for potent inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) could help develop safer drugs and more effective pharmacoenhancers. We utilize a rational inhibitor design to decipher structure-activity relationships in analogues of ritonavir, a highly potent CYP3A4 inhibitor marketed as pharmacoenhancer. Analysis of compounds with the R1 side-group as phenyl or naphthalene and R2 as indole or naphthalene in different stereo configuration showed that (i) analogues with the R2-naphthalene tend to bind tighter and inhibit CYP3A4 more potently than the R2-phenyl/indole containing counterparts; (ii) stereochemistry becomes a more important contributing factor, as the bulky side-groups limit the ability to optimize protein-ligand interactions; (iii) the relationship between the R1/R2 configuration and preferential binding to CYP3A4 is complex and depends on the side-group functionality/interplay and backbone spacing; and (iv) three inhibitors, 5a-b and 7d, were superior to ritonavir (IC50 of 0.055-0.085 muM vs. 0.130 muM, respectively).
		+
		+	An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4.,Samuels ER, Sevrioukova IF Bioorg Med Chem. 2020 Mar 15;28(6):115349. doi: 10.1016/j.bmc.2020.115349. Epub, 2020 Jan 31. PMID:32044230<ref>PMID:32044230</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6une" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sevrioukova, I F]]		[[Category: Sevrioukova, I F]]

OCA at 08:13, 5 February 2020

2020-02-05T08:13:06Z

←Older revision		Revision as of 08:13, 5 February 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6une is ~~ON HOLD until Paper Publication~~	+	==Human CYP3A4 bound to an inhibitor==
-		+	<StructureSection load='6une' size='340' side='right'caption='[[6une]], [[Resolution\|resolution]] 2.55Å' scene=''>
-	~~Authors~~: ~~Sevrioukova~~, I.F.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6une]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UNE FirstGlance]. <br>
-	~~Description~~: ~~Human CYP3A4 bound to~~ an ~~inhibitor~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QES:tert-butyl+[(2R)-1-(1H-indol-3-yl)-3-{[(2S)-3-oxo-2-(phenylamino)-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}propan-2-yl]carbamate'>QES</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6une FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6une OCA], [http://pdbe.org/6une PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6une RCSB], [http://www.ebi.ac.uk/pdbsum/6une PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6une ProSAT]</span></td></tr>
-	[[Category: Sevrioukova, I.F]]	+	</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Sevrioukova, I F]]
		+	[[Category: Complex]]
		+	[[Category: Cyp3a4]]
		+	[[Category: Inhibitor]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 07:37, 30 October 2019

2019-10-30T07:37:12Z

←Older revision		Revision as of 07:37, 30 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6une is ON HOLD	+	The entry 6une is ON HOLD until Paper Publication

	Authors: Sevrioukova, I.F.		Authors: Sevrioukova, I.F.

OCA: Protected "6une" [edit=sysop:move=sysop]

2019-10-23T05:12:15Z

Protected "6une" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:12, 23 October 2019

OCA: New page: '''Unreleased structure''' The entry 6une is ON HOLD Authors: Sevrioukova, I.F. Description: Human CYP3A4 bound to an inhibitor Category: Unreleased Structures [[Category: Sevriouk...

2019-10-23T05:12:13Z

New page: '''Unreleased structure''' The entry 6une is ON HOLD Authors: Sevrioukova, I.F. Description: Human CYP3A4 bound to an inhibitor Category: Unreleased Structures [[Category: Sevriouk...

New page

'''Unreleased structure'''

The entry 6une is ON HOLD

Authors: Sevrioukova, I.F.

Description: Human CYP3A4 bound to an inhibitor
[[Category: Unreleased Structures]]
[[Category: Sevrioukova, I.F]]