6bdk - Revision history

OCA at 14:38, 4 October 2023

OCA — Wed, 04 Oct 2023 14:38:46 GMT

←Older revision		Revision as of 14:38, 4 October 2023
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	<StructureSection load='6bdk' size='340' side='right'caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>		<StructureSection load='6bdk' size='340' side='right'caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bdk]] 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=6BDK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BDK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bdk]] 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=6BDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BDK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DJ1:tert-butyl+[(2S)-1-{[(2R)-2-(cyclopentylamino)-3-oxo-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}-3-(1H-indol-3-yl)propan-2-yl]carbamate'>DJ1</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]] 2.67Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bcz\|6bcz]], [[6bd5\|6bd5]], [[6bd6\|6bd6]], [[6bd7\|6bd7]], [[6bd8\|6bd8]], [[6bdh\|6bdh]], [[6bdi\|6bdi]], [[6bdm\|6bdm]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DJ1:tert-butyl+[(2S)-1-{[(2R)-2-(cyclopentylamino)-3-oxo-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}-3-(1H-indol-3-yl)propan-2-yl]carbamate'>DJ1</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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'>[https://proteopedia.org/fgij/fg.htm?mol=6bdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bdk OCA], [https://pdbe.org/6bdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bdk RCSB], [https://www.ebi.ac.uk/pdbsum/6bdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bdk 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=6bdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bdk OCA], [~~http~~://pdbe.org/6bdk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6bdk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6bdk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6bdk 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sevrioukova, I]]	+	[[Category: Sevrioukova I]]
-	~~[[Category: Cytochrome p450]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 16:05, 29 January 2020

OCA — Wed, 29 Jan 2020 16:05:32 GMT

←Older revision		Revision as of 16:05, 29 January 2020
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	== 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 ==
		+	Structure-function relationships of nine rationally designed ritonavir-like compounds were investigated to better understand the ligand binding and inhibitory mechanism in human drug-metabolizing cytochrome P450 3A4 (CYP3A4). The analogs had a similar backbone and pyridine and tert-butyloxycarbonyl (Boc) as the heme-ligating and terminal groups, respectively. N-Isopropyl, N-cyclopentyl, or N-phenyl were the R1-side group substituents alone (compounds 5a-c) or in combination with phenyl or indole at the R2 position (8a-c and 8d-f subseries, respectively). Our experimental and structural data indicate that (i) for all analogs, a decrease in the dissociation constant (Ks) coincides with a decrease in IC50, but no relation with other derived parameters is observed; (ii) an increase in the R1 volume, hydrophobicity, and aromaticity markedly lowers Ks and IC50, whereas the addition of aromatic R2 has a more pronounced positive effect on the inhibitory potency than the binding strength; (iii) the ligands' association mode is strongly influenced by the mutually dependent R1-R2 interplay, but the R1-mediated interactions are dominant and define the overall conformation in the active site; (iv) formation of a strong H-bond with Ser119 is a prerequisite for potent CYP3A4 inhibition; and (v) the strongest inhibitor in the series, the R1-phenyl/R2-indole containing 8f (Ks and IC50 of 0.08 and 0.43 muM, respectively), is still less potent than ritonavir, even under conditions that prevent the mechanism based inactivation of CYP3A4. Crystallographic data were essential for better understanding and interpretation of the experimental results, and suggested how the inhibitor design could be further optimized.
		+
		+	Inhibition of Human CYP3A4 by Rationally Designed Ritonavir-Like Compounds: Impact and Interplay of the Side Group Functionalities.,Samuels ER, Sevrioukova I Mol Pharm. 2018 Jan 2;15(1):279-288. doi: 10.1021/acs.molpharmaceut.7b00957. Epub, 2017 Dec 12. PMID:29232137<ref>PMID:29232137</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6bdk" style="background-color:#fffaf0;"></div>

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

OCA at 09:19, 18 December 2019

OCA — Wed, 18 Dec 2019 09:19:22 GMT

←Older revision		Revision as of 09:19, 18 December 2019
Line 1:		Line 1:

	==Crystal structure of human CYP3A4 bound to an inhibitor==		==Crystal structure of human CYP3A4 bound to an inhibitor==
-	<StructureSection load='6bdk' size='340' side='right' caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>	+	<StructureSection load='6bdk' size='340' side='right'caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6bdk]] 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=6BDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BDK FirstGlance]. <br>		<table><tr><td colspan='2'>[[6bdk]] 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=6BDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BDK FirstGlance]. <br>
Line 11:		Line 11:
	== 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>
		+
		+	==See Also==
		+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 16:		Line 19:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Sevrioukova, I]]		[[Category: Sevrioukova, I]]
	[[Category: Cytochrome p450]]		[[Category: Cytochrome p450]]

OCA at 08:25, 17 January 2018

OCA — Wed, 17 Jan 2018 08:25:18 GMT

←Older revision		Revision as of 08:25, 17 January 2018
Line 3:		Line 3:
	<StructureSection load='6bdk' size='340' side='right' caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>		<StructureSection load='6bdk' size='340' side='right' caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bdk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BDK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bdk]] 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=6BDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BDK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DJ1:tert-butyl+[(2S)-1-{[(2R)-2-(cyclopentylamino)-3-oxo-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}-3-(1H-indol-3-yl)propan-2-yl]carbamate'>DJ1</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=DJ1:tert-butyl+[(2S)-1-{[(2R)-2-(cyclopentylamino)-3-oxo-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}-3-(1H-indol-3-yl)propan-2-yl]carbamate'>DJ1</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">[[6bcz\|6bcz]], [[6bd5\|6bd5]], [[6bd6\|6bd6]], [[6bd7\|6bd7]], [[6bd8\|6bd8]], [[6bdh\|6bdh]], [[6bdi\|6bdi]], [[6bdm\|6bdm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bcz\|6bcz]], [[6bd5\|6bd5]], [[6bd6\|6bd6]], [[6bd7\|6bd7]], [[6bd8\|6bd8]], [[6bdh\|6bdh]], [[6bdi\|6bdi]], [[6bdm\|6bdm]]</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=6bdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bdk OCA], [http://pdbe.org/6bdk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bdk RCSB], [http://www.ebi.ac.uk/pdbsum/6bdk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bdk 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=6bdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bdk OCA], [http://pdbe.org/6bdk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bdk RCSB], [http://www.ebi.ac.uk/pdbsum/6bdk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bdk ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Sevrioukova, I]]		[[Category: Sevrioukova, I]]
	[[Category: Cytochrome p450]]		[[Category: Cytochrome p450]]

OCA at 07:03, 13 December 2017

OCA — Wed, 13 Dec 2017 07:03:46 GMT

←Older revision		Revision as of 07:03, 13 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6bdk is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Crystal structure of human CYP3A4 bound to an inhibitor==
-		+	<StructureSection load='6bdk' size='340' side='right' caption='[[6bdk]], [[Resolution\|resolution]] 2.67Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6bdk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BDK FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DJ1:tert-butyl+[(2S)-1-{[(2R)-2-(cyclopentylamino)-3-oxo-3-{[(pyridin-3-yl)methyl]amino}propyl]sulfanyl}-3-(1H-indol-3-yl)propan-2-yl]carbamate'>DJ1</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bcz\|6bcz]], [[6bd5\|6bd5]], [[6bd6\|6bd6]], [[6bd7\|6bd7]], [[6bd8\|6bd8]], [[6bdh\|6bdh]], [[6bdi\|6bdi]], [[6bdm\|6bdm]]</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=6bdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bdk OCA], [http://pdbe.org/6bdk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bdk RCSB], [http://www.ebi.ac.uk/pdbsum/6bdk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bdk ProSAT]</span></td></tr>
		+	</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: Sevrioukova, I]]
		+	[[Category: Cytochrome p450]]
		+	[[Category: Inhibitor]]
		+	[[Category: Monooxygenase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 06:31, 8 November 2017

OCA — Wed, 08 Nov 2017 06:31:34 GMT

←Older revision		Revision as of 06:31, 8 November 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 01 Nov 2017 04:57:26 GMT

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

←Older revision

Revision as of 04:57, 1 November 2017

OCA: New page: '''Unreleased structure''' The entry 6bdk is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 01 Nov 2017 04:57:24 GMT

New page: '''Unreleased structure''' The entry 6bdk is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6bdk is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]