Asunto(s)
Bioquímica/historia , Investigación/tendencias , Animales , Bioquímica/tendencias , Biología/historia , Biología/tendencias , Fenómenos Fisiológicos Celulares , Células , Química Orgánica , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Biología Molecular , Plantas , Investigación/historiaRESUMEN
The highly abundant GTP binding protein elongation factor Tu (EF-Tu) fulfills multiple roles in bacterial protein biosynthesis. Phage-displayed peptides with high affinity for EF-Tu were selected from a library of approximately 4.7 x 10(11) different peptides. The lack of sequence homology among the identified EF-Tu ligands demonstrates promiscuous peptide binding by EF-Tu. Homolog shotgun scanning of an EF-Tu ligand was used to dissect peptide molecular recognition by EF-Tu. All homolog shotgun scanning selectants bound to EF-Tu with higher affinity than the starting ligand. Thus, homolog shotgun scanning can simultaneously optimize binding affinity and rapidly provide detailed structure activity relationships for multiple side chains of a polypeptide ligand. The reported peptide ligands do not compete for binding to EF-Tu with various antibiotic EF-Tu inhibitors, and could identify an EF-Tu peptide binding site distinct from the antibiotic inhibitory sites.
