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New page: '''Unreleased structure''' The entry 6ex1 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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==Crystal structure of human carbonic anhydrase I in complex with the 4-[(3S)-3 benzyl-4-(4-sulfamoylbenzoyl)piperazine -1-carbonyl]benzene-1-sulfonamide inhibitor== | |||
<StructureSection load='6ex1' size='340' side='right' caption='[[6ex1]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ex1]] 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=6EX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EX1 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=N19:4-[(3~{R})-3-(phenylmethyl)piperazin-1-yl]carbonylbenzenesulfonamide'>N19</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=6ex1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ex1 OCA], [http://pdbe.org/6ex1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ex1 RCSB], [http://www.ebi.ac.uk/pdbsum/6ex1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ex1 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> | ||
<div class="pdbe-citations 6ex1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Carbonate dehydratase]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Chiapponi, D]] | |||
[[Category: Chiaramonte, N]] | [[Category: Chiaramonte, N]] | ||
[[Category: Ferraroni, M]] | [[Category: Ferraroni, M]] | ||
[[Category: Supuran, C T]] | |||
[[Category: Lyase]] | |||
Latest revision as of 11:11, 10 October 2018
Crystal structure of human carbonic anhydrase I in complex with the 4-[(3S)-3 benzyl-4-(4-sulfamoylbenzoyl)piperazine -1-carbonyl]benzene-1-sulfonamide inhibitorCrystal structure of human carbonic anhydrase I in complex with the 4-[(3S)-3 benzyl-4-(4-sulfamoylbenzoyl)piperazine -1-carbonyl]benzene-1-sulfonamide inhibitor
Structural highlights
Function[CAH1_HUMAN] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.[1] Publication Abstract from PubMedTwo 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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