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PDBsum entry 3ibn

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Lyase/lyase inhibitor PDB id
3ibn
Jmol
Contents
Protein chain
258 a.a.
Ligands
O60
HGB
Metals
_ZN
_CL
Waters ×171

References listed in PDB file
Key reference
Title Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-Sulfamate adducts with isozymes ii and IX as a platform for designing tight-Binding, More isoform-Selective inhibitors.
Authors R.M.Vitale, V.Alterio, A.Innocenti, J.Y.Winum, S.M.Monti, G.De simone, C.T.Supuran.
Ref. J Med Chem, 2009, 52, 5990-5998. [DOI no: 10.1021/jm900641r]
PubMed id 19731956
Abstract
Two approaches were used to design inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): the tail and the ring approaches. Aliphatic sulfamates constitute a class of CA inhibitors (CAIs) that cannot be classified in either one of these categories. We report here the detailed inhibition profile of four such compounds against isoforms CAs I-XIV, the first crystallographic structures of these compounds in adduct with isoform II, and molecular modeling studies for their interaction with hCA IX. Aliphatic monosulfamates/bis-sulfamates were nanomolar inhibitors of hCAs II, IX, and XII, unlike aromatic/heterocyclic sulfonamides that promiscuously inhibit most CA isozymes with low nanomolar affinity. The bis-sulfamates incorporating 8 or 10 carbon atoms showed higher affinity for the tumor-associated hCA IX compared to hCA II, whereas the opposite was true for the monosulfamates. The explanation for their interaction with CA active site furnishes insights for obtaining compounds with increased affinity/selectivity for various isozymes.
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