6h38: Difference between revisions
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The | ==The crystal structure of human carbonic anhydrase VII in complex with 4-[(4-fluorophenyl)methyl]-1-piperazinyl]benzenesulfonamide.== | ||
<StructureSection load='6h38' size='340' side='right'caption='[[6h38]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6h38]] 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=6H38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H38 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]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FKK:4-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]carbonylbenzenesulfonamide'>FKK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6h38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h38 OCA], [https://pdbe.org/6h38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h38 RCSB], [https://www.ebi.ac.uk/pdbsum/6h38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h38 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAH7_HUMAN CAH7_HUMAN] Reversible hydration of carbon dioxide. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Guided by the crystal structure of 4-(3,4-dihydroquinolin-1(2H)-ylcarbonyl)benzenesulfonamide 3 in complex with hCA II (PDB code 4Z0Q), a novel series of cycloalkylamino-1-carbonylbenzenesulfonamides was designed and synthesized. Thus, we replaced the quinoline ring with an azepine/piperidine/piperazine nucleus and introduced further modifications on cycloalkylamine nucleus by means the installation of hydrophobic/hydrophilic functionalities able to establish additional contacts in the middle area of the enzyme cavity. Among the synthesized compounds, the derivatives 7a, 7b, 8b exhibited a remarkable inhibition for hCA II and the brain-expressed hCA VII in subnanomolar range. The binding of these molecules to the target enzymes was characterized by means of a crystallographic analysis, providing a clear snapshot of the most important interactions established by this class of inhibitors into the hCA II and hCA VII catalytic site. Notably, our results showed that the benzylpiperazine tail of compound 8b is oriented both in hCA II and in hCA VII toward a poorly explored region of the active site. These features should be further investigated for the design of new isoform selective CA inhibitors. | |||
Exploring structural properties of potent human carbonic anhydrase inhibitors bearing a 4-(cycloalkylamino-1-carbonyl)benzenesulfonamide moiety.,Buemi MR, Di Fiore A, De Luca L, Angeli A, Mancuso F, Ferro S, Monti SM, Buonanno M, Russo E, De Sarro G, De Simone G, Supuran CT, Gitto R Eur J Med Chem. 2018 Dec 1;163:443-452. doi: 10.1016/j.ejmech.2018.11.073. PMID:30530195<ref>PMID:30530195</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6h38" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: De Luca | *[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Angeli A]] | ||
[[Category: | [[Category: Buemi MR]] | ||
[[Category: | [[Category: Buonanno M]] | ||
[[Category: De Luca L]] | |||
[[Category: De Sarro G]] | |||
[[Category: De Simone G]] | |||
[[Category: Di Fiore A]] | |||
[[Category: Ferro S]] | |||
[[Category: Gitto R]] | |||
[[Category: Mancuso F]] | |||
[[Category: Monti SM]] | |||
[[Category: Russo E]] | |||
[[Category: Supuran CT]] | |||
Latest revision as of 12:02, 9 October 2024
The crystal structure of human carbonic anhydrase VII in complex with 4-[(4-fluorophenyl)methyl]-1-piperazinyl]benzenesulfonamide.The crystal structure of human carbonic anhydrase VII in complex with 4-[(4-fluorophenyl)methyl]-1-piperazinyl]benzenesulfonamide.
Structural highlights
FunctionCAH7_HUMAN Reversible hydration of carbon dioxide. Publication Abstract from PubMedGuided by the crystal structure of 4-(3,4-dihydroquinolin-1(2H)-ylcarbonyl)benzenesulfonamide 3 in complex with hCA II (PDB code 4Z0Q), a novel series of cycloalkylamino-1-carbonylbenzenesulfonamides was designed and synthesized. Thus, we replaced the quinoline ring with an azepine/piperidine/piperazine nucleus and introduced further modifications on cycloalkylamine nucleus by means the installation of hydrophobic/hydrophilic functionalities able to establish additional contacts in the middle area of the enzyme cavity. Among the synthesized compounds, the derivatives 7a, 7b, 8b exhibited a remarkable inhibition for hCA II and the brain-expressed hCA VII in subnanomolar range. The binding of these molecules to the target enzymes was characterized by means of a crystallographic analysis, providing a clear snapshot of the most important interactions established by this class of inhibitors into the hCA II and hCA VII catalytic site. Notably, our results showed that the benzylpiperazine tail of compound 8b is oriented both in hCA II and in hCA VII toward a poorly explored region of the active site. These features should be further investigated for the design of new isoform selective CA inhibitors. Exploring structural properties of potent human carbonic anhydrase inhibitors bearing a 4-(cycloalkylamino-1-carbonyl)benzenesulfonamide moiety.,Buemi MR, Di Fiore A, De Luca L, Angeli A, Mancuso F, Ferro S, Monti SM, Buonanno M, Russo E, De Sarro G, De Simone G, Supuran CT, Gitto R Eur J Med Chem. 2018 Dec 1;163:443-452. doi: 10.1016/j.ejmech.2018.11.073. PMID:30530195[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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