Conformational studies on synthetic peptides reproducing the dibasic processing site of pro-ocytocin-neurophysin.
Synthetic peptides reproducing the proteolytic processing site of pro-ocytocin were studied by different spectroscopic techniques, including circular dichroism, Fourier transform infrared absorption, and mono and bidimensional nuclear magnetic resonance, in order to ascertain the possible role of three-dimensional structure in the recognition process by maturation enzymes. Experimental results were compared with energy minimization calculations and suggest that: (i) the region situated on the N-terminus of the Lys-Arg doublet may form a beta-turn; (ii) the sequential organization of the residues participating in the beta-turn determines the privileged relative orientation of the basic amino acid sidechains and the subtype of turn; and (iii) the peptide segment situated on the C-terminal side of the dibasic doublet may assume a helix arrangement. These findings, in spite of the limitations connected to the flexibility of linear peptides, seem to substantiate the hypothesis that structural motifs around the cleavage site could be important for recognition and processing. however, a straightforward correlation between details of the secondary structure and the in vitro reactivity toward a putative convertase is not yet possible.
Di Bello
C
C
Institute of Industrial Chemistry, University of Padova, Italy.
Simonetti
M
M
Dettin
M
M
Paolillo
L
L
D'Aurla
G
G
Falcigno
L
L
Saviano
M
M
Scatturin
A
A
Vertuani
G
G
Cohen
P
P
D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009481:Neurophysins / Q000737:chemistry* / Q000378:metabolism; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D009481:Neurophysins; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D001127:Arginine Vasopressin; D010121:Oxytocin; C046278:oxytocin, Gly-Lys-Arg-