6y3c: Difference between revisions
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<StructureSection load='6y3c' size='340' side='right'caption='[[6y3c]], [[Resolution|resolution]] 3.36Å' scene=''> | <StructureSection load='6y3c' size='340' side='right'caption='[[6y3c]], [[Resolution|resolution]] 3.36Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6y3c]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6y3c]] 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=6Y3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y3C FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.361Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</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'>[https://proteopedia.org/fgij/fg.htm?mol=6y3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y3c OCA], [https://pdbe.org/6y3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y3c RCSB], [https://www.ebi.ac.uk/pdbsum/6y3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y3c ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PGH1_HUMAN PGH1_HUMAN] Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined to an R/Rfree of 20.82/26.37, at 3.36 A resolution. hCOX-1 structure provides a detailed picture of the enzyme active site and the residues crucial for inhibitor/substrate binding and catalytic activity. We compared hCOX-1 crystal structure with the ovine COX-1 and human COX-2 structures by using metrics based on Cartesian coordinates, backbone dihedral angles, and solvent accessibility coupled with multivariate methods. Differences and similarities among structures are discussed, with emphasis on the motifs responsible for the diversification of the various enzymes (primary structure, stability, catalytic activity, and specificity). The structure of hCOX-1 represents an essential step towards the development of new and more selective COX-1 inhibitors of enhanced therapeutic potential. | |||
Three-dimensional structure of human cyclooxygenase (hCOX)-1.,Miciaccia M, Belviso BD, Iaselli M, Cingolani G, Ferorelli S, Cappellari M, Loguercio Polosa P, Perrone MG, Caliandro R, Scilimati A Sci Rep. 2021 Feb 22;11(1):4312. doi: 10.1038/s41598-021-83438-z. PMID:33619313<ref>PMID:33619313</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6y3c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Belviso BD]] | |||
[[Category: Belviso | [[Category: Caliandro R]] | ||
[[Category: Caliandro | [[Category: Ferorelli S]] | ||
[[Category: Ferorelli | [[Category: Iaselli M]] | ||
[[Category: Iaselli | [[Category: Miciaccia M]] | ||
[[Category: Miciaccia | [[Category: Perrone MG]] | ||
[[Category: Perrone | [[Category: Scilimati A]] | ||
[[Category: Scilimati | |||