Recurring main-chain anion-binding motifs in short polypeptides: nests.
A novel tripeptide motif called a nest has recently been described in proteins with the function of binding anionic, or partially anionic, atoms such as carbonyl O atoms. In the present work, a search for nests in small polypeptides stored in the Cambridge Structural Database is reported. 37 unique examples were found: over half form part of hydrogen-bond arrangements resembling those in proteins, such as Schellman/paperclip loop motifs, various types of beta-turn and Asx-turns or Ser/Thr-turns, while a third are in novel situations, some involving binding to anionic groups from other molecules within the crystal complex. An example is the antibiotic vancomycin, which incorporates a prominent nest forming part of a peptide-binding site. This nest binds the carboxylate of the C-terminal D-alanine of the bacterial cell-wall precursor peptide, thereby inhibiting the final step of bacterial cell-wall synthesis. As in proteins, a number of nests occur in short peptides with an alternating glycine/L-amino-acid sequence but, uniquely to non-ribosomally synthesized short peptides, several nests within them are constructed from alternating D- and L-amino acids, and such sequences seem to specially favour nests.
Milner-White
E James
EJ
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland. j.milner-white@bio.gla.uk
Nissink
J Willemm
JW
Allen
Frank H
FH
Duddy
William J
WJ
D020816:Amino Acid Motifs; D000838:Anions / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D030562:Databases, Protein; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D018583:Pliability; D011487:Protein Conformation
D000838:Anions; D010455:Peptides