title: X-ray crystallographic studies reveal that the incorporation of spacer groups in carbonic anhydrase inhibitors causes alternate binding modes.
abstract: Human carbonic anhydrases (CAs) are well studied targets for the development of inhibitors for pharmaceutical applications. The crystal structure of human CA II has been determined in complex with two CA inhibitors (CAIs) containing conventional sulfonamide and thiadiazole moieties separated by a -CF2- or -CHNH2- spacer group. The structures presented here reveal that these spacer groups allow novel binding modes for the thiadiazole moiety compared with conventional CAIs.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: S Zoë
authors.initials: SZ
authors.lastname: Fisher
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Govindasamy
authors.forename: Nicholas
authors.initials: N
authors.lastname: Boyle
authors.forename: Mavis
authors.initials: M
authors.lastname: Agbandje-McKenna
authors.forename: David N
authors.initials: DN
authors.lastname: Silverman
authors.forename: G Michael
authors.initials: GM
authors.lastname: Blackburn
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
mesh_terms: D001665:Binding Sites; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D002256:Carbonic Anhydrases