Conformational analysis of PKI(5-22)amide, the active inhibitory fragment of the inhibitor protein of the cyclic AMP-dependent protein kinase.
Fourier-transform i.r. spectroscopy, 1H-n.m.r. spectroscopy and X-ray scattering were used to study the conformation and shape of the peptide PKI(5-22)amide, which contains the active site of the inhibitor protein of the cyclic AMP-dependent protein kinase [Cheng, Van Pattern, Smith & Walsh (1985) Biochem. J. 231, 655-661]. The X-ray-scattering solution studies show that the peptide has a compact structure with Rg 0.9 nm (9.0 A) and a linear maximum dimension of 2.5 nm (25A). Compatible with this, Fourier-transform i.r. and n.m.r. determinations indicate that the peptide contains approx. 26% alpha-helix located in the N-terminal one-third of the molecule. This region contains the phenylalanine residue that is one essential recognition determinant for high-affinity binding to the protein kinase catalytic site.
Reed
J
J
Institute of Experimental Pathology, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
De Ropp
J S
JS
Trewhella
J
J
Glass
D B
DB
Liddle
W K
WK
Bradbury
E M
EM
Kinzel
V
V
Walsh
D A
DA
D000577:Amides; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology; D006859:Hydrogen; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000577:Amides; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C015482:protein kinase modulator; D006859:Hydrogen