title: Three-dimensional view of the surface motif associated with the P-loop structure: cis and trans cases of convergent evolution.
abstract: Here we identify the determinants of the nucleotide-binding ability associated with the P-loop-containing proteins, inferring their functional importance from their structural convergence to a unique three- dimensional (3D) motif. (1) A new surface 3D pattern is identified for the P-loop nucleotide-binding region, which is more selective than the corresponding sequence pattern; (2) the signature displays one residue that we propose is the determinant for the guanine-binding ability (the residues aligned to ras D119; this residue is known to be important only in the G-proteins, we extend the prediction to all the other P-loop- containing proteins); and (3) two cases of convergent evolution at the molecular level are highlighted in the analysis of the active site: the positive charge aligned to ras K117 and the arginine residues aligned to the GAP arginine finger. The analysis of the residues conserved on protein surfaces allows one to identify new functional or evolutionary relationships among protein structures that would not be detectable by conventional sequence or structure comparison methods.
authors.affiliation: Centro di Bioinformatica Molecolare, Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, Rome, 00133, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Via
authors.forename: F
authors.initials: F
authors.lastname: Ferrè
authors.forename: B
authors.initials: B
authors.lastname: Brannetti
authors.forename: A
authors.initials: A
authors.lastname: Valencia
authors.forename: M
authors.initials: M
authors.lastname: Helmer-Citterich
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001216:Asparagine / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D055672:Static Electricity; D013379:Substrate Specificity
chemical_list: D001216:Asparagine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D001120:Arginine; D009703:Nucleoside-Phosphate Kinase; D012260:Ribonucleases; D019204:GTP-Binding Proteins; D000409:Alanine