7uff - Revision history

OCA at 14:44, 13 August 2026

2026-08-13T14:44:52Z

← Older revision		Revision as of 14:44, 13 August 2026
Line 5:		Line 5:
	<table><tr><td colspan='2'>[[7uff]] is a 2 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=7UFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7uff]] is a 2 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=7UFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFF FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.7Å</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]] 2.7Å</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=NYF:N-(2-~~oxo~~-2-{[(2S)-1-{[(2R)-1-~~oxo~~-3-phenyl-1-{[3-(pyridin-3-yl)~~propyl]amino}~~propan-2-yl]sulfanyl}-3-~~phenylpropan~~-2-yl]amino}ethyl)pyridine-3-carboxamide'>NYF</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=NYF:~{N}-[2-oxidanylidene-2-[[(2~{S})-1-[(2~{R})-1-oxidanylidene-3-phenyl-1-(3-pyridin-3-ylpropylamino)propan-2-yl]sulfanyl-3-phenyl-propan-2-yl]amino]ethyl]pyridine-3-carboxamide'>NYF</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7uff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uff OCA], [https://pdbe.org/7uff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uff RCSB], [https://www.ebi.ac.uk/pdbsum/7uff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uff 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=7uff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uff OCA], [https://pdbe.org/7uff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uff RCSB], [https://www.ebi.ac.uk/pdbsum/7uff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uff 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 ==~~
	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 7uff" style="background-color:#fffaf0;"></div>~~

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

OCA at 17:15, 18 October 2023

2023-10-18T17:15:35Z

← Older revision		Revision as of 17:15, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7uff]] is a 2 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=7UFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7uff]] is a 2 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=7UFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFF 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=NYF:N-(2-oxo-2-{[(2S)-1-{[(2R)-1-oxo-3-phenyl-1-{[3-(pyridin-3-yl)propyl]amino}propan-2-yl]sulfanyl}-3-phenylpropan-2-yl]amino}ethyl)pyridine-3-carboxamide'>NYF</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.7Å</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=NYF:N-(2-oxo-2-{[(2S)-1-{[(2R)-1-oxo-3-phenyl-1-{[3-(pyridin-3-yl)propyl]amino}propan-2-yl]sulfanyl}-3-phenylpropan-2-yl]amino}ethyl)pyridine-3-carboxamide'>NYF</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7uff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uff OCA], [https://pdbe.org/7uff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uff RCSB], [https://www.ebi.ac.uk/pdbsum/7uff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uff 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=7uff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uff OCA], [https://pdbe.org/7uff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uff RCSB], [https://www.ebi.ac.uk/pdbsum/7uff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uff 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 ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7uff" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7uff" 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

2022-09-08T04:16:58Z

← Older revision		Revision as of 04:16, 8 September 2022
Line 1:		Line 1:

	==Human CYP3A4 bound to an inhibitor==		==Human CYP3A4 bound to an inhibitor==
	<StructureSection load='7uff' size='340' side='right'caption='[[7uff]]' scene=''>		<StructureSection load='7uff' size='340' side='right'caption='[[7uff]], [[Resolution\|resolution]] 2.70Å' 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=7UFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7uff]] is a 2 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=7UFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFF 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=7uff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uff OCA], [https://pdbe.org/7uff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uff RCSB], [https://www.ebi.ac.uk/pdbsum/7uff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uff 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=NYF:N-(2-oxo-2-{[(2S)-1-{[(2R)-1-oxo-3-phenyl-1-{[3-(pyridin-3-yl)propyl]amino}propan-2-yl]sulfanyl}-3-phenylpropan-2-yl]amino}ethyl)pyridine-3-carboxamide'>NYF</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7uff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uff OCA], [https://pdbe.org/7uff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uff RCSB], [https://www.ebi.ac.uk/pdbsum/7uff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uff 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 7uff" 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

2022-07-27T18:05:25Z

← Older revision		Revision as of 18:05, 27 July 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

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

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

2022-03-30T09:35:33Z

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

← Older revision	Revision as of 09:35, 30 March 2022
(No difference)

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

2022-03-30T09:35:32Z

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

New page

'''Unreleased structure'''

The entry 7uff is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]