title: Structural convergence in the active sites of a family of catalytic antibodies.
abstract: The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed. The high resolution structures account for catalysis by transition state stabilization, and in all three antibodies a tyrosine residue participates in the oxyanion hole. Despite significant conformational differences in their combining sites, the three antibodies, which are the most efficient among those elicited, achieve catalysis in essentially the same mode, suggesting that evolution for binding to a single TSA followed by screening for catalysis lead to antibodies with structural convergence.
authors.affiliation: Laboratoire d'Enzymologie et de Biochimie Structurales, CNRS, 91198 Gif sur Yvette Cedex, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Charbonnier
authors.forename: B
authors.initials: B
authors.lastname: Golinelli-Pimpaneau
authors.forename: B
authors.initials: B
authors.lastname: Gigant
authors.forename: D S
authors.initials: DS
authors.lastname: Tawfik
authors.forename: R
authors.initials: R
authors.lastname: Chap
authors.forename: D G
authors.initials: DG
authors.lastname: Schindler
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: B S
authors.initials: BS
authors.lastname: Green
authors.forename: Z
authors.initials: Z
authors.lastname: Eshhar
authors.forename: M
authors.initials: M
authors.lastname: Knossow
mesh_terms: D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D019143:Evolution, Molecular; D006241:Haptens / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D063065:Organophosphonates / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014443:Tyrosine / Q000737:chemistry
chemical_list: D017151:Antibodies, Catalytic; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D063065:Organophosphonates; D014443:Tyrosine