7ufd - Revision history

OCA at 17:15, 18 October 2023

2023-10-18T17:15:30Z

←Older revision		Revision as of 17:15, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7ufd]] 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=7UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFD FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ufd]] 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=7UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFD FirstGlance]. <br>
-	</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=T0K:(2S)-3-phenyl-2-({(2S)-3-phenyl-2-[3-(pyridin-3-yl)propanamido]propyl}sulfanyl)-N-[2-(pyridin-3-yl)ethyl]propanamide'>T0K</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]] 2.9Å</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=T0K:(2S)-3-phenyl-2-({(2S)-3-phenyl-2-[3-(pyridin-3-yl)propanamido]propyl}sulfanyl)-N-[2-(pyridin-3-yl)ethyl]propanamide'>T0K</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=7ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufd OCA], [https://pdbe.org/7ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufd RCSB], [https://www.ebi.ac.uk/pdbsum/7ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufd 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=7ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufd OCA], [https://pdbe.org/7ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufd RCSB], [https://www.ebi.ac.uk/pdbsum/7ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufd 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7ufd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7ufd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 04:16, 8 September 2022

2022-09-08T04:16:52Z

←Older revision		Revision as of 04:16, 8 September 2022
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	==Human CYP3A4 bound to an inhibitor==		==Human CYP3A4 bound to an inhibitor==
-	<StructureSection load='7ufd' size='340' side='right'caption='[[7ufd]]' scene=''>	+	<StructureSection load='7ufd' size='340' side='right'caption='[[7ufd]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ufd]] 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=7UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFD FirstGlance]. <br>
-	</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=7ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufd OCA], [https://pdbe.org/7ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufd RCSB], [https://www.ebi.ac.uk/pdbsum/7ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufd ProSAT]</span></td></tr>	+	</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=T0K:(2S)-3-phenyl-2-({(2S)-3-phenyl-2-[3-(pyridin-3-yl)propanamido]propyl}sulfanyl)-N-[2-(pyridin-3-yl)ethyl]propanamide'>T0K</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=7ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufd OCA], [https://pdbe.org/7ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufd RCSB], [https://www.ebi.ac.uk/pdbsum/7ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufd ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Controlled inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) is utilized to boost bioavailability of anti-viral and immunosuppressant pharmaceuticals. We investigate structure-activity relationships (SARs) in analogues of ritonavir, a potent CYP3A4 inhibitor marketed as pharmacoenhancer, to determine structural elements required for potent inhibition and whether the inhibitory potency can be further improved via a rational structure-based design. This study investigated eight (series VI) inhibitors differing in head- and end-moieties and their respective linkers. SAR analysis revealed the multifactorial regulation of inhibitory strength, with steric constraints imposed on the tethered heme-ligating moiety being a key factor. Minimization of these constraints by changing the linkers' length/flexibility and N-heteroatom position strengthened heme coordination and markedly improved binding and/or inhibitory strength. Impact of the end-pyridine attachment was not uniform due to influence of other determinants controlling the ligand-binding mode. This interplay between pharmacophoric determinants and the end-group enlargement can be used for further inhibitor optimization.
		+
		+	Interaction of CYP3A4 with Rationally Designed Ritonavir Analogues: Impact of Steric Constraints Imposed on the Heme-Ligating Group and the End-Pyridine Attachment.,Samuels ER, Sevrioukova IF Int J Mol Sci. 2022 Jun 30;23(13). pii: ijms23137291. doi: 10.3390/ijms23137291. PMID:35806297<ref>PMID:35806297</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ufd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sevrioukova IF]]		[[Category: Sevrioukova IF]]

OCA at 18:05, 27 July 2022

2022-07-27T18:05:20Z

←Older revision		Revision as of 18:05, 27 July 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7ufd ~~is ON HOLD~~	+	==Human CYP3A4 bound to an inhibitor==
-		+	<StructureSection load='7ufd' size='340' side='right'caption='[[7ufd]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFD FirstGlance]. <br>
-	~~Description~~:	+	</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=7ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufd OCA], [https://pdbe.org/7ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufd RCSB], [https://www.ebi.ac.uk/pdbsum/7ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufd ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Sevrioukova IF]]

OCA: Protected "7ufd" [edit=sysop:move=sysop]

2022-03-30T09:35:29Z

Protected "7ufd" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:35, 30 March 2022

OCA: New page: '''Unreleased structure''' The entry 7ufd is ON HOLD Authors: Description: Category: Unreleased Structures

2022-03-30T09:35:28Z

New page: '''Unreleased structure''' The entry 7ufd is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7ufd is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]