Proline brackets and identification of potential functional sites in proteins: toxins to therapeutics.
Protein toxins induce their specific pharmacological effects through protein protein interaction. Identification of these protein-protein interaction sites could lead to prototypes of highly specific therapeutic agents. However, deciphering the structure function relationships of protein toxins and locating the functional sites is a difficult, tedious and cumbersome task. We recently developed a novel predictive method to identify potential protein protein interaction sites directly from the amino acid sequence of a protein (R. M. Kini and H. J. Evans (1996) FEBS Lett. 385, 81-86) based on the presence of proline residues, a common residue found predominantly in the flanking segments of protein-protein interaction sites (R. M. Kini and H. J. Evans (1996) Biochem. Biophys. Res. Commun. 212, 1115-1124). It is a simple and straight-forward method. This review describes the new method and its application to solve structure function relationships of protein toxins. The method is useful in identifying functional sites in toxins, despite the subtle and complex nature of their structure function relationships and saves significant amounts of time and money.
Kini
R M
RM
Bioscience Centre, Faculty of Science, National University of Singapore, Singapore.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D004546:Elapid Venoms / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry* / Q000494:pharmacology
D000596:Amino Acids; D002121:Calcium Channel Blockers; D004546:Elapid Venoms; D014118:Toxins, Biological; C067971:calciseptine; D011392:Proline