6EQU

X-Ray crystal structure of the human carbonic anhydrase II adduct with a membrane-impermeant inhibitor

Summary for 6EQU

• Entry DOI: 10.2210/pdb6equ/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, 4-[2-(2,4,6-triphenylpyridin-1-ium-1-yl)ethyl]benzenesulfonamide, ... (4 entities in total)
• Functional Keywords: human carbonic anhydrase ii, membrane-impermeant inhibitor, complex, lyase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29903.14

Authors

Alterio, V.,De Simone, G.,Esposito, D. (deposition date: 2017-10-15, release date: 2017-12-13, Last modification date: 2024-01-17)

Primary citation

Alterio, V.,Esposito, D.,Monti, S.M.,Supuran, C.T.,De Simone, G.
Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor.
J Enzyme Inhib Med Chem, 33:151-157, 2018

PubMed Abstract: Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report the structural characterization of the adduct that a triphenylpyridinium derivative forms with hCA II, showing that the substitution of the pyridinium ring plays a key role in determining the conformation of the inhibitor in the active site and consequently the binding affinity to the enzyme. These findings open new perspectives on the basic structural requirements for designing sulfonamide CAIs with a selective inhibition profile.

PubMed: 29199489
DOI: 10.1080/14756366.2017.1405263

Experimental method

X-RAY DIFFRACTION (1.65 Å)