A conformational study in solution of pro-somatostatin fragments by NMR and computational methods

✍ Scribed by Lucia Falcigno; Franca Fraternali; Daniela M. Manduca; Gabriella D'Auria; Mario Simonetti; Carlo Di Bello; Livio Paolillo

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 188 KB
• Volume: 4
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(199808)4:5<305::aid-psc149>3.0.co;2-s

✦ Synopsis

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 i-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 i-turn is displaced by one residue and involves the Ala 5 -Arg 8 segment. This observation may explain the lack of recognition by the maturation enzyme.