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3tzi

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X-ray crystal structure of arachidonic acid bound in the cyclooxygenase channel of G533V murine COX-2

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Retrieved from "http://52.214.119.220/wiki/index.php/3tzi"

Categories: Large Structures | Mus musculus | Malkowski MG | Vecchio AJ

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 ==X-ray crystal structure of arachidonic acid bound in the cyclooxygenase channel of G533V murine COX-2==
-<StructureSection load='3tzi' size='340' side='right' caption='[[3tzi]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+<StructureSection load='3tzi' size='340' side='right'caption='[[3tzi]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3tzi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TZI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TZI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3tzi]] 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=3TZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TZI 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 2.15&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hs5|3hs5]], [[3krk|3krk]], [[3qh0|3qh0]], [[3mdl|3mdl]], [[1diy|1diy]], [[1cvu|1cvu]]</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<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 Mus musculus])</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=3tzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tzi OCA], [https://pdbe.org/3tzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tzi RCSB], [https://www.ebi.ac.uk/pdbsum/3tzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tzi ProSAT]</span></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=3tzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tzi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tzi RCSB], [http://www.ebi.ac.uk/pdbsum/3tzi PDBsum]</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>
+[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;">
-== Publication Abstract from PubMed ==
-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.
-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>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
 ==See Also==
-*[[Cyclooxygenase|Cyclooxygenase]]
+*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Prostaglandin-endoperoxide synthase]]
+[[Category: Malkowski MG]]
-[[Category: Malkowski, M G]]
+[[Category: Vecchio AJ]]
-[[Category: Vecchio, A J]]
-[[Category: Monotopic membrane protein]]
-[[Category: N-glycosylation]]
-[[Category: Oxidoreductase]]

3tzi

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Current revision

X-ray crystal structure of arachidonic acid bound in the cyclooxygenase channel of G533V murine COX-2

Structural highlights

Function

See Also

References

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