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A conformational study in solution of pro‐somatostatin fragments by NMR and computational methods
Author(s) -
Falcigno Lucia,
Fraternali Franca,
Manduca Daniela M.,
D'Auria Gabriella,
Simonetti Mario,
Di Bello Carlo,
Paolillo Livio
Publication year - 1998
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/(sici)1099-1387(199808)4:5<305::aid-psc149>3.0.co;2-s
Subject(s) - chemistry , dibasic acid , cleavage (geology) , residue (chemistry) , stereochemistry , enzyme , alanine , active site , peptide , nuclear magnetic resonance spectroscopy , amino acid residue , biochemistry , amino acid , peptide sequence , biology , organic chemistry , paleontology , fracture (geology) , gene
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 β ‐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 β ‐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. © 1998 European Peptide Society and John Wiley & Sons, Ltd.