2QO8

Crystal structure of the complex of hcaii with an indane-sulfonamide inhibitor

Summary for 2QO8

• Entry DOI: 10.2210/pdb2qo8/pdb
• Related: 1CA2 2QOA 2QP6
• Descriptor: Carbonic anhydrase 2, ZINC ION, MERCURIBENZOIC ACID, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase ii, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00918
• Total number of polymer chains: 1
• Total formula weight: 30067.63

Authors

D'Ambrosio, K.,De Simone, G. (deposition date: 2007-07-20, release date: 2008-01-22, Last modification date: 2023-08-30)

Primary citation

D'Ambrosio, K.,Masereel, B.,Thiry, A.,Scozzafava, A.,Supuran, C.T.,De Simone, G.
Carbonic Anhydrase Inhibitors: Binding of Indanesulfonamides to the Human Isoform II.
Chemmedchem, 3:473-477, 2007

PubMed Abstract: Indanesulfonamides are interesting lead compounds for designing selective inhibitors of the different isoforms of the zinc enzyme Carbonic Anhydrase (CA). Herein, we report for the first time the X-ray crystal structure of two such derivatives, namely indane-5-sulfonamide and indane-2-valproylamido-5-sulfonamide, in complex with the physiologically dominant human isoform II. The structural analysis reveals that, although these two inhibitors have quite similar chemical structures, the arrangement of their indane ring within the enzyme active site is significantly diverse. Thus, our findings suggest that the introduction of bulky substituents on the indane-sulfonamide ring may alter the binding mode of this potent class of CA inhibitors, although retaining good inhibitory properties. Accordingly, the introduction of bulky tail moieties on the indane-sulfonamide scaffold may represent a powerful strategy to induce a desired physicochemical property to an aromatic sulfonamide or to obtain inhibitors with diverse inhibition profiles and selectivity for various mammalian CAs.

PubMed: 18161740
DOI: 10.1002/cmdc.200700274

Experimental method

X-RAY DIFFRACTION (1.4 Å)