title: Catalysis of decarboxylation by a preorganized heterogeneous microenvironment: crystal structures of abzyme 21D8.
abstract: Antibody 21D8 catalyzes the solvent-sensitive decarboxylation of 3-carboxybenzisoxazoles. The crystal structure of chimeric Fab 21D8 with and without hapten at 1.61 A and 2.10 A, respectively, together with computational analysis, shows how a melange of polar and non-polar sites are exploited to achieve both substrate binding and acceleration of a reaction normally facilitated by purely aprotic dipolar media. The striking similarity of the decarboxylase and a series of unrelated esterase antibodies also highlights the chemical versatility of structurally conserved anion binding sites and the relatively subtle changes involved in fine-tuning the immunoglobulin pocket for recognition of different ligands and catalysis of different reactions.
authors.affiliation: Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hotta
authors.forename: H
authors.initials: H
authors.lastname: Lange
authors.forename: D J
authors.initials: DJ
authors.lastname: Tantillo
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.forename: D
authors.initials: D
authors.lastname: Hilvert
authors.forename: I A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000378:metabolism; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D001666:Binding Sites, Antibody; D002262:Carboxy-Lyases / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002384:Catalysis; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004950:Esterases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007555:Isoxazoles / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D012997:Solvents; D055672:Static Electricity
chemical_list: D000838:Anions; D017151:Antibodies, Catalytic; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007555:Isoxazoles; D008024:Ligands; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D012997:Solvents; C414687:abzyme 21D8; D004950:Esterases; D002262:Carboxy-Lyases