title: The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand.
abstract: It's the water that matters. Pairs of benzo- and perfluorobenzoarylsulfonamide ligands bind to human carbonic anhydrase with a conserved binding geometry, an enthalpy-driven binding, and indistinguishable binding affinities (see picture). These data support the pervasive theory that the lock-and-key model disregards an important component of binding: the water, which fills the binding pocket of the protein and surrounds the ligand.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lockett
authors.forename: Heiko
authors.initials: H
authors.lastname: Lange
authors.forename: Benjamin
authors.initials: B
authors.lastname: Breiten
authors.forename: Annie
authors.initials: A
authors.lastname: Heroux
authors.forename: Woody
authors.initials: W
authors.lastname: Sherman
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Rappoport
authors.forename: Patricia O
authors.initials: PO
authors.lastname: Yau
authors.forename: Philip W
authors.initials: PW
authors.lastname: Snyder
authors.forename: George M
authors.initials: GM
authors.lastname: Whitesides
mesh_terms: D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005459:Fluorides / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry / Q000378:metabolism*; D000096926:Benzenesulfonamides
chemical_list: D002256:Carbonic Anhydrases; D005459:Fluorides; D013449:Sulfonamides; D014867:Water; D000096926:Benzenesulfonamides
keywords: biomolecular recognition; carbonic anhydrase; hydrophobic effect; protein-ligand binding; water