3bl0 | pdb_00003bl0
Carbonic anhydrase inhibitors. Interaction of 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies
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Overview
2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for, its interaction with the 12 catalytically active mammalian carbonic, anhydrase (CA, EC 4.2.1.1) isozymes, CA I-XIV. The compound is a potent, inhibitor of CA IV, VII, IX, XII, and XIII (K(I)s of 0.61-39nM), a medium, potency inhibitor of CA II and VA (K(I)s of 121-438nM), and a weak, inhibitor against the other isoforms (CA III, VB, VI, and XIV), making it, a very interesting candidate for situations in which a strong/selective, inhibition of certain isozymes is needed. The crystal structure of the hCA, II adduct of this sulfonamide revealed interesting interactions between, the inhibitor and the enzyme which are quite different from those observed, in the adducts of CA II with the structurally related aliphatic, derivatives zonisamide, 2-amino-1,3,4-thiadiazolyl-5-difluoromethanesulfonamide, and, 2-dimethylamino-5-[sulfonamido-(aminomethyl)]-1,3,4-thiadiazole reported, earlier.
About this Structure
3BL0 is a Single protein structure of sequence from Homo sapiens with ZN, BL0 and MBO as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Known structural/functional Sites: AC1, AC2 and AC3. Full crystallographic information is available from OCA.
Reference
Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: Kinetic and X-ray crystallographic studies., Temperini C, Cecchi A, Boyle NA, Scozzafava A, Cabeza JE, Wentworth P Jr, Blackburn GM, Supuran CT, Bioorg Med Chem Lett. 2007 Dec 15;. PMID:18162396
Page seeded by OCA on Wed Jan 23 10:59:47 2008
