title: Identification of an allosteric binding site on the transcription factor p53 using a phage-displayed peptide library.
abstract: Monoclonal antibody PAb1620 recognizes a conformational epitope on the transcription factor p53 and, upon binding, allosterically inhibits p53 binding to DNA. A highly diverse (1.5 x 10(10) members) phage-displayed library of peptides containing 40 random amino acids was used to identify the PAb1620 binding site on p53. Panning this library against PAb1620 resulted in three unique peptides which have statistically significant sequence identities with p53 sufficient to identify the binding site as being composed of amino acids 106-113 and 146-156. Based on these results, we propose a mechanism by which PAb1620 can allosterically inhibit p53 binding to DNA through an indirect interaction between the antibody binding site and the L1 loop (amino acids 112-124) of p53, which is a component of the DNA binding region.
authors.affiliation: DGI BioTechnologies, Edison, New Jersey 08818, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Ravera
authors.forename: J
authors.initials: J
authors.lastname: Cárcamo
authors.forename: R
authors.initials: R
authors.lastname: Brissette
authors.forename: A
authors.initials: A
authors.lastname: Alam-Moghé
authors.forename: O
authors.initials: O
authors.lastname: Dedova
authors.forename: W
authors.initials: W
authors.lastname: Cheng
authors.forename: K C
authors.initials: KC
authors.lastname: Hsiao
authors.forename: D
authors.initials: D
authors.lastname: Klebanov
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: P
authors.initials: P
authors.lastname: Tang
authors.forename: A
authors.initials: A
authors.lastname: Blume
authors.forename: W
authors.initials: W
authors.lastname: Mandecki
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001435:Bacteriophages / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA