Abstract
Isoquinolinesulfonamides inhibit human carbonic anhydrases (hCAs) and display selectivity toward therapeutically relevant isozymes. The crystal structure of hCA II in complex with 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamide revealed unusual inhibitor binding. Structural analyses allowed for discerning the fine details of the inhibitor binding mode to the active site, thus providing clues for the future design of even more selective inhibitors for druggable isoforms such as the cancer associated hCA IX and neuronal hCA VII.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carbonic Anhydrase II / antagonists & inhibitors
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Carbonic Anhydrase II / chemistry*
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Carbonic Anhydrase II / metabolism*
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Carbonic Anhydrase Inhibitors / chemistry*
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Carbonic Anhydrase Inhibitors / metabolism*
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Carbonic Anhydrase Inhibitors / pharmacology
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Crystallography, X-Ray
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / chemistry
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Isoenzymes / metabolism
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Isoquinolines / chemistry*
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Isoquinolines / metabolism*
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Isoquinolines / pharmacology
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Models, Molecular
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Protein Binding
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Protein Conformation
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Substrate Specificity
Substances
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Carbonic Anhydrase Inhibitors
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Isoenzymes
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Isoquinolines
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Carbonic Anhydrase II