9r8y

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

spinqualitylabelsall models 9r8y, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9r8y 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 1.95Å Ligands: A1JDL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CAH9_HUMAN Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. Publication Abstract from PubMed Discovery of small-molecule drugs relies on their strong binding affinity compared to nontarget proteins, thus possessing selectivity. Minor chemical structure changes usually exhibit little change in the compound efficacy, with rare exceptions. We developed a series of nearly 50 ortho-substituted benzenesulfonamides and experimentally measured their interactions with the 12 catalytically active human carbonic anhydrase (CA) isozymes. Inhibitors were designed using seven different substituent groups, including 4-sulfanyl-substituted 3-sulfamoyl benzoates and benzamides, 4-sulfinyl-substituted 3-sulfamoyl benzoates and benzamides, 4-sulfonyl-substituted 3-sulfamoyl benzoates and benzamides, and 4-amino-substituted benzamides. The oxidation state of sulfur at the ortho position significantly influenced the compound's affinity for CAIX, a target for anticancer drugs, demonstrating affinities hundreds of thousands of times stronger than related compounds. Coupled with X-ray crystal structures and molecular docking, the relationship between structure and thermodynamics offers insights into how small changes in the structure lead to significant changes in affinity for drug design. Affinity and Selectivity of Protein-Ligand Recognition: A Minor Chemical Modification Changes Carbonic Anhydrase Binding Profile.,Zaksauskas A, Paketuryte-Latve V, JankuÌ naite A, Capkauskaite E, Becart Y, Smirnov A, Pospisilova K, Leitans J, Brynda J, Kazaks A, Baranauskiene L, Manakova E, Grazulis S, Kairys V, Tars K, Rezacova P, Matulis D J Med Chem. 2025 Aug 28;68(16):17752-17773. doi: 10.1021/acs.jmedchem.5c01421. , Epub 2025 Aug 13. PMID:40801814 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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