6ofy - Revision history

OCA at 07:10, 11 October 2023

2023-10-11T07:10:10Z

←Older revision		Revision as of 07:10, 11 October 2023
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	<StructureSection load='6ofy' size='340' side='right'caption='[[6ofy]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6ofy' size='340' side='right'caption='[[6ofy]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ofy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6OFY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ofy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OFY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACD:ARACHIDONIC+ACID'>ACD</scene>, <scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=COH:PROTOPORPHYRIN+IX+CONTAINING+CO'>COH</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACD:ARACHIDONIC+ACID'>ACD</scene>, <scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=COH:PROTOPORPHYRIN+IX+CONTAINING+CO'>COH</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6ofy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofy OCA], [~~http~~://pdbe.org/6ofy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ofy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ofy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofy 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=6ofy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofy OCA], [https://pdbe.org/6ofy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ofy RCSB], [https://www.ebi.ac.uk/pdbsum/6ofy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofy ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PGH2_MOUSE PGH2_MOUSE]] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.<ref>PMID:12925531</ref> <ref>PMID:20463020</ref> <ref>PMID:20810665</ref> <ref>PMID:21489986</ref>	+	[https://www.uniprot.org/uniprot/PGH2_MOUSE PGH2_MOUSE] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.<ref>PMID:12925531</ref> <ref>PMID:20463020</ref> <ref>PMID:20810665</ref> <ref>PMID:21489986</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 6ofy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ofy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cyclooxygenase 3D structures\|Cyclooxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Prostaglandin-endoperoxide synthase~~]]	+	[[Category: Mus musculus]]
-	[[Category: Malkowski~~, M G]]~~	+	[[Category: Malkowski MG]]
-	~~[[Category: Arachidonic acid cyclooxygenase prostaglandin endoperoxide synthase]]~~	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 08:02, 5 February 2020

2020-02-05T08:02:21Z

←Older revision		Revision as of 08:02, 5 February 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6ofy is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of Arachidonic Acid bound to V349I murine COX-2==
		+	<StructureSection load='6ofy' size='340' side='right'caption='[[6ofy]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ofy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OFY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACD:ARACHIDONIC+ACID'>ACD</scene>, <scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=COH:PROTOPORPHYRIN+IX+CONTAINING+CO'>COH</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] </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=6ofy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofy OCA], [http://pdbe.org/6ofy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ofy RCSB], [http://www.ebi.ac.uk/pdbsum/6ofy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofy ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PGH2_MOUSE PGH2_MOUSE]] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.<ref>PMID:12925531</ref> <ref>PMID:20463020</ref> <ref>PMID:20810665</ref> <ref>PMID:21489986</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aspirin and Celebrex are well-known time-dependent inhibitors of the cyclooxygenases (COX). Molecular dynamics simulations suggest that Arg-513 and Leu-531 contribute to the structural mechanisms of COX inhibition. We used mutagenesis and functional analyses to characterize how substitutions at these positions influence time-dependent inhibition by aspirin and Celebrex. We show that substitutions of Leu-531 with asparagine and phenylalanine significantly attenuate time-dependent inhibition of COX-2 by these drugs. The introduction of side chain bulk, rigidity, and charge would disrupt the formation of the initial noncovalent complex, in the case of aspirin, and the "high-affinity" binding state, in the case of Celebrex. Substitution of Arg-513 with histidine (the equivalent residue in COX-1) resulted in a 2-fold potentiation of aspirin inhibition, in support of the hypothesis that the presence of histidine in COX-1 lowers the activation barrier associated with the formation of the initial noncovalent enzyme-inhibitor complex. As a corollary, we previously hypothesized that the flexibility associated with Leu-531 contributes to the binding of arachidonic acid (AA) to acetylated COX-2 to generate 15R-hydroxyeicosatetraenoic acid (15R-HETE). We determined the X-ray crystal structure of AA bound to Co(3+)-protoporphyrin IX-reconstituted V349I murine COX-2 (muCOX-2). V349I muCOX-2 was utilized as a surrogate to trap AA in a conformation leading to 15R-HETE. AA binds in a C-shaped pose, facilitated by the rotation of the Leu-531 side chain. Ile-349 is positioned to sterically shield antarafacial oxygen addition at carbon-15 in a manner similar to that proposed for the acetylated Ser-530 side chain.

-	~~Authors: Malkowski~~, M.G.	+	Arg-513 and Leu-531 Are Key Residues Governing Time-Dependent Inhibition of Cyclooxygenase-2 by Aspirin and Celebrex.,Dong L, Anderson AJ, Malkowski MG Biochemistry. 2019 Sep 24;58(38):3990-4002. doi: 10.1021/acs.biochem.9b00659., Epub 2019 Sep 9. PMID:31469551<ref>PMID:31469551</ref>

-	~~Description: Crystal Structure~~ of ~~Arachidonic Acid bound to V349I murine COX~~-2	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Malkowski, M.G]]	+	<div class="pdbe-citations 6ofy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Prostaglandin-endoperoxide synthase]]
		+	[[Category: Malkowski, M G]]
		+	[[Category: Arachidonic acid cyclooxygenase prostaglandin endoperoxide synthase]]
		+	[[Category: Membrane protein]]
		+	[[Category: Oxidoreductase]]

OCA at 13:09, 29 January 2020

2020-01-29T13:09:53Z

←Older revision		Revision as of 13:09, 29 January 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Malkowski, M.G.		Authors: Malkowski, M.G.

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

2019-04-10T05:32:33Z

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

←Older revision

Revision as of 05:32, 10 April 2019

OCA: New page: '''Unreleased structure''' The entry 6ofy is ON HOLD Authors: Malkowski, M.G. Description: Crystal Structure of Arachidonic Acid bound to V349I murine COX-2 [[Category: Unreleased Stru...

2019-04-10T05:32:31Z

New page: '''Unreleased structure''' The entry 6ofy is ON HOLD Authors: Malkowski, M.G. Description: Crystal Structure of Arachidonic Acid bound to V349I murine COX-2 [[Category: Unreleased Stru...

New page

'''Unreleased structure'''

The entry 6ofy is ON HOLD

Authors: Malkowski, M.G.

Description: Crystal Structure of Arachidonic Acid bound to V349I murine COX-2
[[Category: Unreleased Structures]]
[[Category: Malkowski, M.G]]