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PDBsum entry 2qp6

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Lyase PDB id
2qp6
Jmol
Contents
Protein chain
258 a.a.
Ligands
MBO
MB1
Metals
_ZN
_CL
_HG
Waters ×357

References listed in PDB file
Key reference
Title Carbonic anhydrase inhibitors: bioreductive nitro-Containing sulfonamides with selectivity for targeting the tumor associated isoforms IX and XII.
Authors K.D'Ambrosio, R.M.Vitale, J.M.Dogné, B.Masereel, A.Innocenti, A.Scozzafava, G.De simone, C.T.Supuran.
Ref. J Med Chem, 2008, 51, 3230-3237. [DOI no: 10.1021/jm800121c]
PubMed id 18481843
Abstract
2-Substituted-5-nitro-benzenesulfonamides incorporating a large variety of secondary/tertiary amines were explored as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), with the aim of designing bioreductive inhibitors targeting the hypoxia overexpressed, tumor-associated isozymes. The compounds were ineffective inhibitors of the cytosolic isoform I, showed a better inhibition of the physiologically relevant CA II (KIs of 8.8-4975 nM), and strongly inhibited the tumor-associated CA IX and XII (KIs of 5.4-653 nM). Some of these compounds showed excellent selectivity ratios for the inhibition of the tumor-associated isozymes over the cytosolic ones (in the range of 10-1395). The X-ray crystal structure of the adduct of hCA II with the lead molecule 2-chloro-5-nitro-benzenesulfonamide as well as molecular modeling studies for interaction with hCA IX afforded a better understanding of factors governing the discrimination of the two isoforms for this type of bioreductive compound targeting specifically hypoxic tumors.
PROCHECK
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