Molecular recognition templates of peptides: driving force for molecular evolution of peptide transporters.
Small peptides derived from protein hydrolysis occur ubiquitously. To utilize these structurally diverse compounds, organisms possess generic peptide transporters for di- (Dpp), tri- (Tpp), and oligopeptides (Opp). Using conformational analysis, we describe the predominant conformers of di-, tri-, and oligopeptides in water; dipeptides occur as nine main groups, defined by specific combinations of torsional angles. The molecular recognition templates (MRTs) of substrates for Dpp and Tpp comprise distinct groups of dipeptide conformers plus folded tripeptide conformers with matching spatial distribution of recognition features; for Opp, the MRT involves specific oligopeptide conformers with extended backbones. For any peptide, the proportion of its conformers in a particular MRT correlates with its relative binding and transport by each transporter. Thus, peptide transporters have evolved complementary specificities to optimize utilization of the universal peptide pool. The general applicability of MRTs should facilitate rational design and targeting of peptide-based prodrugs.
Payne
J W
JW
School of Biological Sciences, University of Wales Bangor, Bangor, Gwynedd, LL57 2UW, United Kingdom. j.w.payne@bangor.ac.uk
Grail
B M
BM
Marshall
N J
NJ
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
D002352:Carrier Proteins; D004151:Dipeptides; D009842:Oligopeptides