3tzi

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[[Image:3tzi.png|left|200px]]
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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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<StructureSection load='3tzi' size='340' side='right' caption='[[3tzi]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</td></tr><tr><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><br>
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<tr><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>
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<tr><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>
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<tr><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><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>
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<table>
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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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{{STRUCTURE_3tzi| PDB=3tzi | SCENE= }}
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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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===X-ray crystal structure of arachidonic acid bound in the cyclooxygenase channel of G533V murine COX-2===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_22637474}}
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==See Also==
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*[[Cyclooxygenase|Cyclooxygenase]]
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==About this Structure==
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== References ==
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[[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].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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<ref group="xtra">PMID:022637474</ref><references group="xtra"/>
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Prostaglandin-endoperoxide synthase]]
[[Category: Prostaglandin-endoperoxide synthase]]

Revision as of 05:57, 5 June 2014

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

3tzi, resolution 2.15Å

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