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PDBsum entry 2h15

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Lyase PDB id
2h15
Jmol
Contents
Protein chain
256 a.a.
Ligands
B19
Metals
_ZN
_HG
Waters ×182

References listed in PDB file
Key reference
Title Carbonic anhydrase inhibitors: clash with ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme ii, Exemplified by the crystal structure of the topiramate sulfamide analogue.
Authors J.Y.Winum, C.Temperini, K.El cheikh, A.Innocenti, D.Vullo, S.Ciattini, J.L.Montero, A.Scozzafava, C.T.Supuran.
Ref. J Med Chem, 2006, 49, 7024-7031. [DOI no: 10.1021/jm060807n]
PubMed id 17125255
Abstract
The sulfamide analogue of the antiepileptic drug topiramate is a 210 times less potent inhibitor of isozyme II of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) compared to topiramate but effectively inhibits isozymes CA VA, VB, VII, XIII, and XIV (KI in the range of 21-35 nM). Its weak binding to CA II is due to a clash between one methyl group of the inhibitor and Ala65 and may be exploited for the drug design of compounds with lower affinity for this ubiquitous isozyme, as Ala65 is unique to CA II. As shown by X-ray crystallography, the sulfamide analogue binds to CA II with the deprotonated sulfamide moiety coordinated to Zn(II) and with the organic scaffold making an extended network of hydrogen bonds with Thr199, Gln92, His94, Asn62, and Thr200. Its binding to this isozyme is more similar to that of topiramate and quite different from that of the topiramate cyclic sulfate analogue RWJ-37947.
PROCHECK
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 Headers