7nc4: Difference between revisions
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==Crystal structure of human carbonic anhydrase VII (hCA VII) in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.== | |||
<StructureSection load='7nc4' size='340' side='right'caption='[[7nc4]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7nc4]] 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=7NC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NC4 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=U7Z:4-[4-(2-chlorophenyl)carbonylpiperazin-1-yl]carbonylbenzenesulfonamide'>U7Z</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=7nc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nc4 OCA], [https://pdbe.org/7nc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nc4 RCSB], [https://www.ebi.ac.uk/pdbsum/7nc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nc4 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 == | |||
To tackle the challenge of isoform selectivity, we explored the entrance of the cavity for selected druggable human Carbonic Anhydrases (hCAs). Based on X-ray crystallographic studies on the 4-(4-(2-chlorobenzoyl)piperazine-1-carbonyl)benzenesulfonamide in complex with the brain expressed hCA VII (PDB code: 7NC4), a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides has been developed. To evaluate their capability to fit the hCA VII catalytic cavity, the newer benzenesulfonamides were preliminary investigated by means of docking simulations. Then, this series of thirteen benzenesulfonamides was synthesized and tested against selected druggable hCAs. Among them, the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showed remarkable affinity towards hCA VII (Ki: 4.3 nM) and good selectivity over the physiologically widespread hCA I when compared to Topiramate (TPM). | |||
Design, synthesis and biochemical evaluation of novel carbonic anhydrase inhibitors triggered by structural knowledge on hCA VII.,Mancuso F, Di Fiore A, De Luca L, Angeli A, De Simone G, Supuran CT, Gitto R Bioorg Med Chem. 2021 Jun 17;44:116279. doi: 10.1016/j.bmc.2021.116279. PMID:34216985<ref>PMID:34216985</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7nc4" style="background-color:#fffaf0;"></div> | ||
[[Category: De Simone | |||
==See Also== | |||
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: De Simone G]] | |||
[[Category: Di Fiore A]] | |||
Latest revision as of 15:32, 1 February 2024
Crystal structure of human carbonic anhydrase VII (hCA VII) in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.Crystal structure of human carbonic anhydrase VII (hCA VII) in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.
Structural highlights
FunctionCAH7_HUMAN Reversible hydration of carbon dioxide. Publication Abstract from PubMedTo tackle the challenge of isoform selectivity, we explored the entrance of the cavity for selected druggable human Carbonic Anhydrases (hCAs). Based on X-ray crystallographic studies on the 4-(4-(2-chlorobenzoyl)piperazine-1-carbonyl)benzenesulfonamide in complex with the brain expressed hCA VII (PDB code: 7NC4), a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides has been developed. To evaluate their capability to fit the hCA VII catalytic cavity, the newer benzenesulfonamides were preliminary investigated by means of docking simulations. Then, this series of thirteen benzenesulfonamides was synthesized and tested against selected druggable hCAs. Among them, the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showed remarkable affinity towards hCA VII (Ki: 4.3 nM) and good selectivity over the physiologically widespread hCA I when compared to Topiramate (TPM). Design, synthesis and biochemical evaluation of novel carbonic anhydrase inhibitors triggered by structural knowledge on hCA VII.,Mancuso F, Di Fiore A, De Luca L, Angeli A, De Simone G, Supuran CT, Gitto R Bioorg Med Chem. 2021 Jun 17;44:116279. doi: 10.1016/j.bmc.2021.116279. PMID:34216985[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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