Abstract
DNA clones for the beta-class carbonic anhydrase (CA, EC 4.2.1.1) of Helicobactor pylori (hpbetaCA) were obtained. A recombinant hpbetaCA protein lacking the N-terminal 15-amino acid residues was produced and purified, representing a catalytically efficient CA. hpbetaCA was strongly inhibited (K(I)s in the range of 24-45 nM) by many sulfonamides/sulfamates, among which acetazolamide, ethoxzolamide, topiramate, and sulpiride, all clinically used drugs. The dual inhibition of alpha- and/or beta-class CAs of H. pylori might represent a useful alternative for the management of gastritis/gastric ulcers, as well as gastric cancer. This is also the first study showing that a bacterial beta-CA can be a drug target.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Carbonic Anhydrase Inhibitors / chemical synthesis*
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Carbonic Anhydrase Inhibitors / pharmacology*
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Carbonic Anhydrases / chemistry*
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Chemistry, Pharmaceutical / methods*
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Cloning, Molecular
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Helicobacter pylori / enzymology*
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Humans
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Molecular Sequence Data
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Stomach Neoplasms / drug therapy
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Stomach Ulcer / drug therapy
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Sulfonamides / antagonists & inhibitors*
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Sulfonamides / chemistry*
Substances
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Carbonic Anhydrase Inhibitors
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Enzyme Inhibitors
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Recombinant Proteins
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Sulfonamides
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Carbonic Anhydrases