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Title
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Refined structure of the aminobenzolamide complex of human carbonic anhydrase II at 1.9 A and sulphonamide modelling of bovine carbonic anhydrase III.
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Authors
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J.Vidgren,
A.Svensson,
A.Liljas.
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Ref.
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Int J Biol Macromol, 1993,
15,
97.
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PubMed id
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Abstract
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The binding of aminobenzolamide to human carbonic anhydrase (HCA II) has been
investigated by X-ray crystallography. The three dimensional atomic structure of
the enzyme inhibitor complex has been refined at 1.9 A resolution. The
crystallographic R-factor is 17.8%. All inhibitor atoms are clearly possible to
identify from the difference electron density map in the active site of the
enzyme. The nitrogen of the sulphonamide group of the inhibitor is bound as a
fourth ligand to the zinc ion, the other three are all histidyl residues. The
binding conformation of the sulphonamide groups is similar to the previously
described sulphonamide inhibitors. One of the oxygens of the outer sulphonamido
group of the inhibitor forms a hydrogen bond to the amino group of Gln 92. The
higher affinity of the benzolamide inhibitor compared with acetazolamide can be
accounted for by the strong aromatic and hydrophobic interactions between the
amino benzene ring of the inhibitor and the residues Phe 131 and Leu 198. In
modelling studies of bovine carbonic anhydrase III (BCA III) it was evident that
Phe 198 prevents an optimal interaction with sulphonamides.
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