2HOC

Crystal structure of the human carbonic anhydrase II in complex with the 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide inhibitor

Summary for 2HOC

• Entry DOI: 10.2210/pdb2hoc/pdb
• Related: 1CA2 2HNC
• Descriptor: Carbonic anhydrase 2, ZINC ION, 5-{[(4-AMINO-3-CHLORO-5-FLUOROPHENYL)SULFONYL]AMINO}-1,3,4-THIADIAZOLE-2-SULFONAMIDE, ... (6 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: 30412.71

Authors

Menchise, V.,Di Fiore, A.,De Simone, G. (deposition date: 2006-07-14, release date: 2006-10-10, Last modification date: 2023-08-30)

Primary citation

Menchise, V.,Simone, G.D.,Fiore, A.D.,Scozzafava, A.,Supuran, C.T.
Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II.
Bioorg.Med.Chem.Lett., 16:6204-6208, 2006

PubMed Abstract: The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the two compounds binds in the canonic manner to the zinc ion and interacts with Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor was positioned in the hydrophobic part of the binding pocket, at van der Waals distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These structures may help in the design of better inhibitors of these widespread zinc-containing enzymes.

PubMed: 17000110
DOI: 10.1016/j.bmcl.2006.09.022

Experimental method

X-RAY DIFFRACTION (2.1 Å)