5gmm: Difference between revisions
New page: '''Unreleased structure''' The entry 5gmm is ON HOLD Authors: Kim, H.T., Hwang, K.Y. Description: Crystal structure of human Carbonic anhydrase I in complex with polmacoxib [[Category:... |
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==Crystal structure of human Carbonic anhydrase I in complex with polmacoxib== | |||
<StructureSection load='5gmm' size='340' side='right'caption='[[5gmm]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5gmm]] is a 2 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=5GMM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GMM FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.003Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=949:4-[3-(3-FLUOROPHENYL)-5,5-DIMETHYL-4-OXIDANYLIDENE-FURAN-2-YL]BENZENESULFONAMIDE'>949</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5gmm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gmm OCA], [https://pdbe.org/5gmm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gmm RCSB], [https://www.ebi.ac.uk/pdbsum/5gmm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gmm ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAH1_HUMAN CAH1_HUMAN] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.<ref>PMID:10550681</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Polmacoxib is not only a selective COX-2 inhibitor but also a potent inhibitor of carbonic anhydrases (CAs). Both CA I and CA II are highly expressed in the GI tract and kidneys, organs that are also thought to be the sites at which selective COX-2 inhibitors show their side effects. By inhibition assays, we show that both CA I and CA II are strongly inhibited by polmacoxib, while CA II also demonstrates direct competition with COX-2. To understand, at the molecular level, how polmacoxib interacts with CA I and II, we solved the first crystal structures of CA I and CA II in complex with polmacoxib, at 2.0 A and 1.8 A, respectively. Interestingly, three polmacoxib molecules bind to the active site of CA I, whereas only one molecule binds CA II. In the active site, the three molecules of polmacoxib organize itself along hydrophobic interaction as "stack-on-formation", and fully occupy a cone-shaped active pocket in CA I. The binding mode of polmacoxib to CA II was found different than its binding to celecoxib and valdecoxib. Our results provide structural insight into inhibition of CA I and CA II by polmacoxib, to assess its potential clinical efficacy. | |||
Structural insight into the inhibition of carbonic anhydrase by the COX-2-selective inhibitor polmacoxib (CG100649).,Kim HT, Cha H, Hwang KY Biochem Biophys Res Commun. 2016 Sep 9;478(1):1-6. doi:, 10.1016/j.bbrc.2016.07.114. Epub 2016 Jul 27. PMID:27475498<ref>PMID:27475498</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Hwang | <div class="pdbe-citations 5gmm" style="background-color:#fffaf0;"></div> | ||
[[Category: Kim | |||
==See Also== | |||
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Hwang KY]] | |||
[[Category: Kim HT]] | |||
Latest revision as of 14:36, 2 August 2023
Crystal structure of human Carbonic anhydrase I in complex with polmacoxibCrystal structure of human Carbonic anhydrase I in complex with polmacoxib
Structural highlights
FunctionCAH1_HUMAN Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.[1] Publication Abstract from PubMedPolmacoxib is not only a selective COX-2 inhibitor but also a potent inhibitor of carbonic anhydrases (CAs). Both CA I and CA II are highly expressed in the GI tract and kidneys, organs that are also thought to be the sites at which selective COX-2 inhibitors show their side effects. By inhibition assays, we show that both CA I and CA II are strongly inhibited by polmacoxib, while CA II also demonstrates direct competition with COX-2. To understand, at the molecular level, how polmacoxib interacts with CA I and II, we solved the first crystal structures of CA I and CA II in complex with polmacoxib, at 2.0 A and 1.8 A, respectively. Interestingly, three polmacoxib molecules bind to the active site of CA I, whereas only one molecule binds CA II. In the active site, the three molecules of polmacoxib organize itself along hydrophobic interaction as "stack-on-formation", and fully occupy a cone-shaped active pocket in CA I. The binding mode of polmacoxib to CA II was found different than its binding to celecoxib and valdecoxib. Our results provide structural insight into inhibition of CA I and CA II by polmacoxib, to assess its potential clinical efficacy. Structural insight into the inhibition of carbonic anhydrase by the COX-2-selective inhibitor polmacoxib (CG100649).,Kim HT, Cha H, Hwang KY Biochem Biophys Res Commun. 2016 Sep 9;478(1):1-6. doi:, 10.1016/j.bbrc.2016.07.114. Epub 2016 Jul 27. PMID:27475498[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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