title: Prediction of homologous binding sites on RB and p107 common for viral oncoproteins and cellular ligands.
abstract: Hydropathic anticomplementarity of amino acids specifies that peptides translated from complementary DNA strands may acquire amphiphilic conformations and bind to each other. This concept has been coined 'Molecular Recognition Theory' (MRT) or 'complementary peptide theory'. Inactivation of retinoblastoma protein (RB), a tumor suppressor gene product, has been shown to be involved in the pathogenesis of many tumors and to be due to either mutation of the RB gene, hyperphosphorylation or complex formation with viral oncoproteins. The viral oncoproteins share a common RB binding motif with cellular ligands. The exact site on RB associating with this common RB binding motif of viral oncoproteins and cellular ligands has not been identified yet. This study is the first to predict putative binding sites on RB and p107, a cellular protein with RB sequence homology, respectively, by using the hydropathic complementarity approach. These sites are residues 649-654 of RB and 657-662 of p107. Moreover, this paper proposes a structure for a potential antineoplastic agent based on the amino acid sequence of the predicted RB binding site. The data presented herein should have important implications both for the understanding of cancer pathophysiology and for the drug design of antineoplastic compounds.
authors.affiliation: Molecular Concepts Research (MCR), Munich, Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Wendtner
authors.forename: R T
authors.initials: RT
authors.lastname: Radulescu
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008024:Ligands; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D008024:Ligands; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; D016160:Retinoblastoma Protein; D014764:Viral Proteins