3MNU

Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron containing aromatic sulfamide with mammalian isoforms I-XV

Summary for 3MNU

• Entry DOI: 10.2210/pdb3mnu/pdb
• Related: 1CA2
• Descriptor: Carbonic anhydrase 2, ZINC ION, MERCURIBENZOIC ACID, ... (7 entities in total)
• Functional Keywords: protein-inhibitor complex, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00918
• Total number of polymer chains: 1
• Total formula weight: 30031.30

Authors

Di Fiore, A.,De Simone, G. (deposition date: 2010-04-22, release date: 2010-06-16, Last modification date: 2023-09-06)

Primary citation

Di Fiore, A.,Monti, S.M.,Innocenti, A.,Winum, J.Y.,De Simone, G.,Supuran, C.T.
Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV.
Bioorg.Med.Chem.Lett., 20:3601-3605, 2010

PubMed Abstract: We investigated the inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms I-XV with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfamide and other simple or sugar sulfamides, a class of less investigated CA inhibitors (CAIs). The crystal structure of the adduct of hCA II with the boron-substituted sulfamide shows the organic scaffold of this compound bound in the hydrophilic half of the active site where it makes a large number of van der Waals contacts with Ile91, Gln92, Val121, Phe131, Leu198, and Thr200. The data here reported provide further insights into sulfamide binding mechanism confirming that this zinc-binding group could be usefully exploited for obtaining new potent and selective CAIs.

PubMed: 20472429
DOI: 10.1016/j.bmcl.2010.04.114

Experimental method

X-RAY DIFFRACTION (1.8 Å)