View source for 6sdt


==HUMAN CARBONIC ANHYDRASE VII IN COMPLEX WITH A SULFONAMIDE INHIBITOR==
<StructureSection load='6sdt' size='340' side='right'caption='[[6sdt]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SDT 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]] 1.94&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L8N:phenyl-(4-sulfamoylphenoxy)phosphinic+acid'>L8N</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=6sdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sdt OCA], [https://pdbe.org/6sdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sdt RCSB], [https://www.ebi.ac.uk/pdbsum/6sdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sdt ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human carbonic anhydrase (CA; EC 4.2.1.1) isoforms II and VII are implicated in neuronal excitation, seizures, and neuropathic pain (NP). Their selective inhibition over off-target CAs is expected to produce an anti-NP action devoid of side effects due to promiscuous CA modulation. Here, a drug design strategy based on the observation of (dis)similarities between the target CA active sites was planned with benzenesulfonamide derivatives and, for the first time, a phosphorus-based linker. Potent and selective CA II/VII inhibitors were identified among the synthesized phenyl(thio)phosphon(amid)ates 3-22. X-ray crystallography depicted the binding mode of phosphonic acid 3 to both CAs II and VII. The most promising derivatives, after evaluation of their stability in acidic media, were tested in a mouse model of oxaliplatin-induced neuropathy. The most potent compound racemic mixture was subjected to HPLC enantioseparation, and the identification of the eutomer, the (S)-enantiomer, allowed to halve the dose totally relieving allodynia in mice.

Phenyl(thio)phosphon(amid)ate Benzenesulfonamides as Potent and Selective Inhibitors of Human Carbonic Anhydrases II and VII Counteract Allodynia in a Mouse Model of Oxaliplatin-Induced Neuropathy.,Nocentini A, Alterio V, Bua S, Micheli L, Esposito D, Buonanno M, Bartolucci G, Osman SM, ALOthman ZA, Cirilli R, Pierini M, Monti SM, Di Cesare Mannelli L, Gratteri P, Ghelardini C, De Simone G, Supuran CT J Med Chem. 2020 May 28;63(10):5185-5200. doi: 10.1021/acs.jmedchem.9b02135. Epub, 2020 May 14. PMID:32364386<ref>PMID:32364386</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6sdt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Alterio V]]
[[Category: De Simone G]]
[[Category: Esposito D]]