4ILX

Structure of human carbonic anhydrase II in complex with an adamantyl sulfonamide inhibitor

Summary for 4ILX

• Entry DOI: 10.2210/pdb4ilx/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: lyase, reversible hydration of carbon dioxide, cytosolic, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00918
• Total number of polymer chains: 1
• Total formula weight: 29608.83

Authors

Biswas, S.,McKenna, R. (deposition date: 2013-01-01, release date: 2013-02-13, Last modification date: 2024-02-28)

Primary citation

Biswas, S.,Carta, F.,Scozzafava, A.,McKenna, R.,Supuran, C.T.
Structural effect of phenyl ring compared to thiadiazole based adamantyl-sulfonamides on carbonic anhydrase inhibition.
Bioorg.Med.Chem., 21:2314-2318, 2013

PubMed Abstract: We investigated the inhibitory activity of sulfonamides incorporating adamantyl moieties against the physiologically relevant human (h) CA (EC 4.2.1.1) isoforms hCA I, II III (cytosolic), IX and XII (transmembrane, tumor-associated). The presence of a benzenesulfonamide instead of an 1,3,4-thiadiazole-sulfonamide fragment in the molecule of CA inhibitors (CAIs) drastically affects both inhibition efficacy and binding within the enzyme active site, as rationalized by means of X-ray crystallography of the adduct of hCA II with 4-(1-adamantylcarboxamidomethyl)benzenesulfonamide. Comparing the present X-ray structure with that of the corresponding 1,3,4-thiadiazole-sulfonamide compound possessing the 1-adamantylcarboxamide moiety, important differences of binding emerged, which explain the highly different inhibition profile of the two compounds against the investigated CA isoforms, most of which (CA I, II, IX and XII) are important drug targets.

PubMed: 23490152
DOI: 10.1016/j.bmc.2013.02.022

Experimental method

X-RAY DIFFRACTION (1.6 Å)