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'''Unreleased structure'''


The entry 30ta is ON HOLD
==Crystal structure of hCA II in complex with 1-Aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide inhibitor==
<StructureSection load='30ta' size='340' side='right'caption='[[30ta]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[30ta]] 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=30TA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=30TA 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]] 1.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1J8Z:(1~{S})-6,7-dimethoxy-1-phenyl-3,4-dihydro-1~{H}-isoquinoline-2-sulfonamide'>A1J8Z</scene>, <scene name='pdbligand=MBO:MERCURIBENZOIC+ACID'>MBO</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=30ta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=30ta OCA], [https://pdbe.org/30ta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=30ta RCSB], [https://www.ebi.ac.uk/pdbsum/30ta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=30ta ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[https://omim.org/entry/259730 259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>
== Function ==
[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human carbonic anhydrase XII (hCA XII) represents an important pharmacological target for different types of cancer. hCA XII plays a crucial role in regulating both extracellular and intracellular pH, thereby influencing cancer cell proliferation, invasion, growth, and metastasis. Although the interaction features of hCA inhibitors (hCAIs) with the catalytic site of distinct hCA isoforms are generally well described, the lack of selectivity remains a major challenge. In a previous work, we have reported a series of 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides displaying weak activity against the ubiquitous hCA I and hCA II, thus emerging as hCAIs that may be free of unwanted side-effects. Herein, further evaluation of their CA inhibitory effects allowed to disclose three potent hCA XII inhibitors at low nanomolar concentrations (K(i) values ranging from 5.5 to 6.5 nM). Additionally, they showed remarkable isoform selectivity compared with the well-known inhibitor SLC-0111, currently in clinical trials as an antitumor agent. Crystallography analyses and computational studies clarified the molecular basis of this behavior and provided valuable insights for the rational design of selective inhibitors targeting hCA XII.


Authors: Di Fiore, A., De Simone, G.
1-Aryl-6,7-Dimethoxy-3,4-Dihydroisoquinoline-2(1H)-Sulfonamides as hCA XII Selective Inhibitors: Experimental and Theoretical Studies to Interrogate the Isoform Selectivity.,Ricci F, Di Fiore A, Angeli A, De Luca L, Mancuso F, Esposito D, De Simone G, Supuran CT, Gitto R ChemMedChem. 2026 Jul 29;21(14):e70390. doi: 10.1002/cmdc.70390. PMID:42493249<ref>PMID:42493249</ref>


Description: Crystal structure of hCA II in complex with 1-Aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide inhibitor
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: De Simone, G]]
<div class="pdbe-citations 30ta" style="background-color:#fffaf0;"></div>
[[Category: Di Fiore, A]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: De Simone G]]
[[Category: Di Fiore A]]
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