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 beta-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.

A conformational study in solution of Pro-Somatostatin fragments by NMR and computational methods

FALCIGNO, LUCIA;D'AURIA, GABRIELLA;
1998

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 beta-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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/373793
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