Bacterial resistance against common antibiotics is an increasing health problem. New pharmaceuticals for the
treatment of infections caused by resistant pathogens are needed. Small proline-rich antimicrobial peptides (PrAMPs)
from insects are known to bind intracellularly to the conventional substrate binding cleft of the E. coli Hsp70 chaperone
DnaK. Furthermore, bactenecins from mammals, members of the cathelicidin family, also contain potential DnaK binding
sites. Crystal structures of bovine and sheep Bac7 in complex with the DnaK substrate binding domain show that the peptides
bind in the forward binding mode with a leucine positioned in the central hydrophobic pocket. In most structures,
proline and arginine residues preceding leucine occupy the hydrophobic DnaK binding sites -1 and -2. Within bovine
Bac7, four potential DnaK binding sites were identified.
Keywords: Antimicrobial peptide, chaperone, peptide binding mode, X-ray crystallography.
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