6evr
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6evr is ON HOLD Authors: Ferraroni, M., Supuran, C.T., Chiapponi, D., Chiaramonte, N. Description: Crystal structure of human carbonic anhydrase I ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human carbonic anhydrase I in complex with the 4-(4 acetyl-3-benzylpiperazine-1 carbonyl)benzene-1-sulfonamide inhibitor== | |
| + | <StructureSection load='6evr' size='340' side='right' caption='[[6evr]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6evr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EVR FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BZW:4-[(3~{S})-4-ethanoyl-3-(phenylmethyl)piperazin-1-yl]carbonylbenzenesulfonamide'>BZW</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </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=6evr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evr OCA], [http://pdbe.org/6evr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6evr RCSB], [http://www.ebi.ac.uk/pdbsum/6evr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6evr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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 == | ||
| + | Two series of 2-benzylpiperazines have been prepared and tested for the inhibition of physiologically relevant isoforms of human carbonic anhydrases (hCA, EC 4.2.1.1). The new compounds carry on one nitrogen atom of the piperazine ring a sulfamoylbenzamide group as zinc-binding moiety, and different alkyl/acyl/sulfonyl groups on the other nitrogen. Regio- and stero-isomers are described. The majority of these compounds showed Ki values in the low-medium nanomolar range against hCA I, II and IV, but not IX. In many instances interaction with the enzyme was enantioselective. The binding mode has been studied by means of X-ray crystallography and molecular modelling. Two compounds, evaluated in rabbit models of glaucoma, were able to significantly reduce intraocular pressure, making them interesting candidates for further studies. | ||
| - | + | 2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and crystallographic studies and in vivo activity for a new class of intraocular pressure lowering agents.,Chiaramonte N, Bua S, Ferraroni M, Nocentini A, Bonardi A, Bartolucci G, Durante M, Lucarini L, Chiapponi D, Dei S, Manetti D, Teodori E, Gratteri P, Masini E, Supuran CT, Romanelli MN Eur J Med Chem. 2018 May 10;151:363-375. doi: 10.1016/j.ejmech.2018.04.002. Epub , 2018 Apr 3. PMID:29635168<ref>PMID:29635168</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6evr" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Carbonate dehydratase]] | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Chiapponi, D]] | [[Category: Chiapponi, D]] | ||
| - | [[Category: | + | [[Category: Chiaramonte, N]] |
[[Category: Ferraroni, M]] | [[Category: Ferraroni, M]] | ||
| + | [[Category: Supuran, C T]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Lyase]] | ||
Current revision
Crystal structure of human carbonic anhydrase I in complex with the 4-(4 acetyl-3-benzylpiperazine-1 carbonyl)benzene-1-sulfonamide inhibitor
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