5vcg - Revision history

OCA at 13:45, 4 October 2023

OCA — Wed, 04 Oct 2023 13:45:56 GMT

←Older revision		Revision as of 13:45, 4 October 2023
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	<StructureSection load='5vcg' size='340' side='right'caption='[[5vcg]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='5vcg' size='340' side='right'caption='[[5vcg]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vcg]] 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=5VCG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VCG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vcg]] 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=5VCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VCG FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene~~>, ~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.2Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[5vc0\|5vc0]], [[5vcc\|5vcc]], [[5vcd\|5vcd]], [[5vce\|5vce]]~~<~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5vcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vcg OCA], [https://pdbe.org/5vcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vcg RCSB], [https://www.ebi.ac.uk/pdbsum/5vcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vcg 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=5vcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vcg OCA], [~~http~~://pdbe.org/5vcg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vcg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vcg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vcg 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: Bromoergocryprine]]~~	+
-	~~[[Category: Cyp3a4]]~~	+
-	~~[[Category: Cysteine mutation]]~~	+
-	~~[[Category: Cytochrome p450]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase-substrate complex~~]]	+

OCA at 09:08, 18 December 2019

OCA — Wed, 18 Dec 2019 09:08:49 GMT

←Older revision		Revision as of 09:08, 18 December 2019
Line 1:		Line 1:

	==Crystal structure of the cysteine depleted CYP3A4 bound to bromoergocryptine==		==Crystal structure of the cysteine depleted CYP3A4 bound to bromoergocryptine==
-	<StructureSection load='5vcg' size='340' side='right' caption='[[5vcg]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='5vcg' size='340' side='right'caption='[[5vcg]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vcg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VCG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VCG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vcg]] 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=5VCG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VCG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">[[5vc0\|5vc0]], [[5vcc\|5vcc]], [[5vcd\|5vcd]], [[5vce\|5vce]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vc0\|5vc0]], [[5vcc\|5vcc]], [[5vcd\|5vcd]], [[5vce\|5vce]]</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=5vcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vcg OCA], [http://pdbe.org/5vcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vcg RCSB], [http://www.ebi.ac.uk/pdbsum/5vcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vcg 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=5vcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vcg OCA], [http://pdbe.org/5vcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vcg RCSB], [http://www.ebi.ac.uk/pdbsum/5vcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vcg ProSAT]</span></td></tr>
	</table>		</table>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5vcg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vcg" 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: Large Structures]]
	[[Category: Sevrioukova, I]]		[[Category: Sevrioukova, I]]
	[[Category: Bromoergocryprine]]		[[Category: Bromoergocryprine]]

OCA at 10:43, 3 August 2017

OCA — Thu, 03 Aug 2017 10:43:12 GMT

←Older revision		Revision as of 10:43, 3 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5vcg is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the cysteine depleted CYP3A4 bound to bromoergocryptine==
		+	<StructureSection load='5vcg' size='340' side='right' caption='[[5vcg]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5vcg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VCG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VCG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=08Y:BROMOERGOCRYPTINE'>08Y</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">[[5vc0\|5vc0]], [[5vcc\|5vcc]], [[5vcd\|5vcd]], [[5vce\|5vce]]</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=5vcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vcg OCA], [http://pdbe.org/5vcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vcg RCSB], [http://www.ebi.ac.uk/pdbsum/5vcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vcg 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human drug-metabolizing cytochrome P450 3A4 (CYP3A4) is a dynamic enzyme with a large and highly malleable active site that can fit structurally diverse compounds. Despite extensive investigations, structure-function relationships and conformational dynamics in CYP3A4 are not fully understood. This study was undertaken to engineer a well-expressed and functionally active cysteine-depleted CYP3A4 that can be used in biochemical and biophysical studies. cDNA codon optimization and screening mutagenesis were utilized to boost the level of bacterial expression of CYP3A4 and identify the least harmful substitutions for all six non-heme-ligating cysteines. The C58A/C64M/C98A/C239T/C377A/C468S (Cys-less) mutant was found to be expressed as highly as the optimized wild-type (opt-WT) CYP3A4. The high-resolution X-ray structures of opt-WT and Cys-less CYP3A4 revealed that gene optimization leads to a different folding in the Phe108 and Phe189 regions and promotes binding of the active site glycerol that interlocks Ser119 and Arg212, critical for ligand association, and the hydrophobic cluster adjacent to Phe108. Crowding and decreased flexibility of the active site, as well as structural alterations observed at the C64M, C239T, and C468S mutational sites, might be responsible for the distinct ligand binding behavior of opt-WT and Cys-less CYP3A4. Nonetheless, the Cys-less mutant could be used for structure-function investigations because it orients bromoergocryptine and ritonavir (a high-affinity substrate and a high-potency inhibitor, respectively) like the WT and has a higher activity toward 7-benzyloxy(4-trifluoromethyl)coumarin.

-	~~Authors:~~ Sevrioukova, I.	+	High-Level Production and Properties of the Cysteine-Depleted Cytochrome P450 3A4.,Sevrioukova IF Biochemistry. 2017 Jun 20;56(24):3058-3067. doi: 10.1021/acs.biochem.7b00334., Epub 2017 Jun 7. PMID:28590129<ref>PMID:28590129</ref>

-	~~Description: Crystal structure~~ of the ~~cysteine depleted CYP3A4 bound to bromoergocryptine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5vcg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Sevrioukova, I]]		[[Category: Sevrioukova, I]]
		+	[[Category: Bromoergocryprine]]
		+	[[Category: Cyp3a4]]
		+	[[Category: Cysteine mutation]]
		+	[[Category: Cytochrome p450]]
		+	[[Category: Monooxygenase]]
		+	[[Category: Oxidoreductase-substrate complex]]

OCA at 10:56, 10 May 2017

OCA — Wed, 10 May 2017 10:56:16 GMT

←Older revision		Revision as of 10:56, 10 May 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5vcg is ON HOLD	+	The entry 5vcg is ON HOLD until Paper Publication

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

OCA: Protected "5vcg" [edit=sysop:move=sysop]

OCA — Wed, 12 Apr 2017 09:53:48 GMT

Protected "5vcg" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:53, 12 April 2017

OCA: New page: '''Unreleased structure''' The entry 5vcg is ON HOLD Authors: Sevrioukova, I. Description: Crystal structure of the cysteine depleted CYP3A4 bound to bromoergocryptine [[Category: Unre...

OCA — Wed, 12 Apr 2017 09:53:46 GMT

New page: '''Unreleased structure''' The entry 5vcg is ON HOLD Authors: Sevrioukova, I. Description: Crystal structure of the cysteine depleted CYP3A4 bound to bromoergocryptine [[Category: Unre...

New page

'''Unreleased structure'''

The entry 5vcg is ON HOLD

Authors: Sevrioukova, I.

Description: Crystal structure of the cysteine depleted CYP3A4 bound to bromoergocryptine
[[Category: Unreleased Structures]]
[[Category: Sevrioukova, I]]