title: Nucleophile recognition as an alternative inhibition mode for benzoic acid based carbonic anhydrase inhibitors.
abstract: A series of hydroxybenzoic acid derivatives have shown inhibitory activity against carbonic anhydrase (CA). X-ray crystallography shows that these molecules inhibit not by binding the active site metal ion but by strong hydrogen bonding to the metal-bound water nucleophile. The binding mode observed for these molecules is distinct when compared to other non-metal-binding CA inhibitors.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Martin
authors.forename: Seth M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D001565:Benzoates / Q000737:chemistry*; D001665:Binding Sites; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D001565:Benzoates; D002257:Carbonic Anhydrase Inhibitors; D007477:Ions; D008670:Metals; D014867:Water; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases