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4e1g

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==X-ray crystal structure of alpha-linolenic acid bound to the cyclooxygenase channel of cyclooxygenase-2==
==X-ray crystal structure of alpha-linolenic acid bound to the cyclooxygenase channel of cyclooxygenase-2==
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<StructureSection load='4e1g' size='340' side='right' caption='[[4e1g]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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<StructureSection load='4e1g' size='340' side='right'caption='[[4e1g]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4e1g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E1G FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4e1g]] 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=4E1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E1G FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LNL:ALPHA-LINOLENIC+ACID'>LNL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tzi|3tzi]], [[3hs5|3hs5]], [[3hs6|3hs6]], [[3hs7|3hs7]], [[3qh0|3qh0]], [[1diy|1diy]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LNL:ALPHA-LINOLENIC+ACID'>LNL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cox-2, Cox2, Pghs-b, Ptgs2, Tis10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1g OCA], [https://pdbe.org/4e1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e1g RCSB], [https://www.ebi.ac.uk/pdbsum/4e1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1g ProSAT]</span></td></tr>
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<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>
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<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=4e1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1g OCA], [http://pdbe.org/4e1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e1g RCSB], [http://www.ebi.ac.uk/pdbsum/4e1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1g ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The cyclooxygenases (COX-1 and COX-2) generate prostaglandin H(2) from arachidonic acid (AA). In its catalytically productive conformation, AA binds within the cyclooxygenase channel with its carboxylate near Arg-120 and Tyr-355 and omega-end located within a hydrophobic groove above Ser-530. While AA is the preferred substrate for both isoforms, COX-2 can oxygenate a broad spectrum of substrates. Mutational analyses have established that an interaction of the carboxylate of AA with Arg-120 is required for high-affinity binding by COX-1, but not COX-2, suggesting that hydrophobic interactions between the omega-end of substrates and cyclooxygenase channel residues play a significant role in COX-2-mediated oxygenation. We used structure-function analyses to investigate the role that Arg-120 and residues lining the hydrophobic groove play in the binding and oxygenation of substrates by murine (mu) COX-2. Mutations to individual amino acids within the hydrophobic groove exhibited decreased rates of oxygenation towards AA, with little effect on binding. R120A muCOX-2 oxygenated 18-carbon omega-6 and omega-3 substrates, albeit at reduced rates, indicating that an interaction with Arg-120 is not required for catalysis. Structural determinations of Co(3+)-protoporphyrin IX reconstituted muCOX-2 with alpha-linolenic acid and G533V muCOX-2 with AA indicate that proper bis-allylic carbon alignment is the major determinant for efficient substrate oxygenation by COX-2. Overall, these findings implicate Arg-120 and hydrophobic groove residues as determinants that govern proper alignment of the bis-allylic carbon below Tyr-385 for catalysis in COX-2 and confirms nuances between COX isoforms that explain substrate promiscuity.
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Investigating substrate promiscuity in cyclooxygenase-2: the role of Arg-120 and residues lining the hydrophobic groove.,Vecchio AJ, Orlando BJ, Nandagiri R, Malkowski MG J Biol Chem. 2012 May 25. PMID:22637474<ref>PMID:22637474</ref>
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==See Also==
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*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4e1g" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Lk3 transgenic mice]]
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[[Category: Large Structures]]
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[[Category: Prostaglandin-endoperoxide synthase]]
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[[Category: Mus musculus]]
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[[Category: Malkowski, M G]]
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[[Category: Malkowski MG]]
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[[Category: Vecchio, A J]]
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[[Category: Vecchio AJ]]
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[[Category: Biological dimer]]
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[[Category: Cox-2]]
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[[Category: Membrane of er]]
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[[Category: Monotopic membrane protein]]
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[[Category: N-glycosylation]]
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[[Category: Oxidoreductase]]
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Current revision

X-ray crystal structure of alpha-linolenic acid bound to the cyclooxygenase channel of cyclooxygenase-2

PDB ID 4e1g

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