title: A conformational study in solution of pro-somatostatin fragments by NMR and computational methods.
abstract: The results of a conformational study by nuclear magnetic spectroscopy and computational methods on a series of point-mutated synthetic peptides, containing 14 amino acid residues and mimicking the region containing the Arg-Lys dibasic cleavage site of pro-somatostatin, have confirmed the possible role of a well defined secondary structure in the recognition phenomenon by processing enzymes. The importance of the residues located near the Arg-Lys dibasic site in the C-terminal region of the pro-hormone for the cleavage of the precursor into somatostatin-14 has been confirmed. The present structural analysis indicates the occurrence of two beta-turns in the 4-7 and 11-14 regions, flanking the cleavage site, for all the peptides recognized as substrates by the processing enzyme. Interestingly, in the point-mutated analogue not processed by the enzyme and containing the replacement of proline by alanine in position 5 the first -turn is displaced by one residue and involves the Ala5-Arg8 segment. This observation may explain the lack of recognition by the maturation enzyme.
authors.affiliation: Department of Chemistry, University of Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Falcigno
authors.forename: F
authors.initials: F
authors.lastname: Fraternali
authors.forename: D M
authors.initials: DM
authors.lastname: Manduca
authors.forename: G
authors.initials: G
authors.lastname: D'Auria
authors.forename: M
authors.initials: M
authors.lastname: Simonetti
authors.forename: C
authors.initials: C
authors.lastname: Di Bello
authors.forename: L
authors.initials: L
authors.lastname: Paolillo
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D017354:Point Mutation; D011487:Protein Conformation; D013004:Somatostatin / Q000737:chemistry* / Q000235:genetics
chemical_list: D010446:Peptide Fragments; D013004:Somatostatin