Identification of a binding site for the anti-inflammatory tripeptide feG.
The mechanism of action of feG, an anti-inflammatory peptide, was explored using data mining, molecular modeling, and enzymatic techniques. The molecular coordinates of protein kinase A (PKA) were used to create six virtual isoforms of protein kinase C (PKCalpha, betaI, betaII, delta, iota, and zeta). With in silico techniques a binding site for feG was identified on PKCbetaI that correlated significantly with a biological activity, the inhibition of intestinal anaphylaxis. Since feG selectively increased the binding of a PKCbetaI antibody, it is proposed that this peptide inhibits the reassociation of the hydrophobic tail of PKCbetaI with its binding site and prevents the enzyme from assuming an inactive conformation.
Mathison
Ronald D
RD
Department of Physiology and Biophysics, Faculty of Medicine, 3330 Hospital Drive NW, The University of Calgary, Calgary, Alta., Canada T2N 4N1. rmathiso@ucalgary.ca
Davison
Joseph S
JS
Metwally
Essam
E
D000595:Amino Acid Sequence; D001665:Binding Sites; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D007527:Isoenzymes; D009842:Oligopeptides; D010455:Peptides; C114891:tripeptide FEG; D011493:Protein Kinase C