9r0u

Three dimensional structure of human carbonic anhydrase XII in complex with sulfonamide

spinqualitylabelsall models 9r0u, resolution 1.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9r0u is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.19Å Ligands: A1H92, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CAH12_HUMAN Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:143860. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat. Function CAH12_HUMAN Reversible hydration of carbon dioxide. Publication Abstract from PubMed The development of selective drug candidate molecules for cancer-related carbonic anhydrase isozymes IX and XII is challenging due to high homology binding sites among 12 catalytically active isozymes. Starting from the trifluorinated benzenesulfonamide with cyclooctylamino substituent at the meta position, we designed and synthesized di-meta-substituted fluorinated benzenesulfonamides with up to 10-fold affinity improvement for CAIX, resulting in low picomolar binders. The resulting CAIX-targeting compounds showed up to 1000-fold selectivity over off-target CA isozymes. The crystal structures of CAIX and CAXII complexes with synthesized compounds revealed detailed insights into protein-ligand interactions and adopted complex conformation. The potential of compounds with reduced off-target effects as possible anticancer drugs is supported by this study. Di-meta-Substituted Fluorinated Benzenesulfonamides as Potent and Selective Anticancer Inhibitors of Carbonic Anhydrase IX and XII.,Vaskevicius A, Zvirblis M, Kurtenoka M, Leitans J, Manakova E, Paketuryte-Latve V, Kvietkauskaite A, Kazaks A, Eimonta V, Cerepenkaite K, Kazokaite-Adomaitiene J, MickeviciuÌ te A, Juozapaitiene V, Tars K, Grazulis S, Matuliene J, Dudutiene V, Shubin K, Matulis D, Zubriene A J Med Chem. 2025 Sep 11;68(17):18389-18406. doi: 10.1021/acs.jmedchem.5c01142. , Epub 2025 Aug 20. PMID:40833423 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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