3V7X

Complex of human carbonic anhydrase II with N-[2-(3,4-dimethoxyphenyl)ethyl]-4-sulfamoylbenzamide

Summary for 3V7X

• Entry DOI: 10.2210/pdb3v7x/pdb
• Related: 3VBD
• Descriptor: Carbonic anhydrase 2, ZINC ION, N-[2-(3,4-dimethoxyphenyl)ethyl]-4-sulfamoylbenzamide, ... (6 entities in total)
• Functional Keywords: 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: 31334.97

Authors

Mader, P.,Brynda, J.,Rezacova, P. (deposition date: 2011-12-22, release date: 2012-04-04, Last modification date: 2023-09-13)

Primary citation

Gitto, R.,Damiano, F.M.,Mader, P.,De Luca, L.,Ferro, S.,Supuran, C.T.,Vullo, D.,Brynda, J.,Rezacova, P.,Chimirri, A.
Synthesis, Structure-Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors.
J.Med.Chem., 55:3891-3899, 2012

PubMed Abstract: A series of arylsulfonamides has been synthesized and investigated for the inhibition of some selected human carbonic anhydrase isoforms. The studied compounds showed significant inhibitory effects in the nanomolar range toward druggable isoforms (hCA VII, hCA IX, and hCA XIV) (K(i) values from 4.8 to 61.7 nM), whereas they generally exhibited significant selectivity over hCA I and hCA II, that are ubiquitous and considered off-target isoforms. On the basis of biochemical data, we herein discussed structure-affinity relationships for this series of arylsulfonamides, suggesting a key role for alkoxy substituents in CA inhibition. Furthermore, X-ray crystal structures of complexes of two active inhibitors (I and 2a) with hCA II allowed us to elucidate the main interactions between the inhibitor and specific amino acid residues within the catalytic site.

PubMed: 22443141
DOI: 10.1021/jm300112w

Experimental method

X-RAY DIFFRACTION (1.03 Å)