Pyrrhocoricin Explained

Pyrrhocoricin
Cas Number:	224569-84-0
Pdb:	5FDV
Uniprot:	P37362

Pyrrhocoricin is a 20-residue long antimicrobial peptide of the firebug Pyrrhocoris apterus.^[1]

Structure and function

Pyrrhocoricin is primarily active against Gram-negative bacteria. The peptide is proline-rich with proline-arginine repeats, as well a critical threonine residue, which is required for activity through O-glycosylation. Like the antimicrobial peptides drosocin and abaecin, pyrrhocoricin binds to the bacterial protein DnaK, inhibiting cell machinery and replication.^[2] Only the L-enantiomer of pyrrhocoricin is active against bacteria.^[3] The action of pyrrhocoricin-like peptides is potentiated by the presence of pore-forming peptides, which facilitates the entry of pyrrhocoricin-like peptides into the bacterial cell.^[4] Proline-rich peptides like Pyrrhocoricin can also bind to microbe ribosomes, preventing protein translation.^[5] In the absence of pore-forming peptides, pyrrhocoricin is taken into the bacteria by the action of bacterial uptake permeases.^[6]

Notes and References

1. Rosengren KJ, Göransson U, Otvos L, Craik DJ . Cyclization of pyrrhocoricin retains structural elements crucial for the antimicrobial activity of the native peptide . Biopolymers . 76 . 5 . 446–58 . 24 February 2019 . 15478127 . 10.1002/bip.20159 . 42355832 .
2. Zahn M, Berthold N, Kieslich B, Knappe D, Hoffmann R, Sträter N . Structural studies on the forward and reverse binding modes of peptides to the chaperone DnaK . Journal of Molecular Biology . 425 . 14 . 2463–79 . July 2013 . 23562829. 10.1016/j.jmb.2013.03.041 .
3. Kragol G, Hoffmann R, Chattergoon MA, Lovas S, Cudic M, Bulet P, Condie BA, Rosengren KJ, Montaner LJ, Otvos L . Identification of crucial residues for the antibacterial activity of the proline-rich peptide, pyrrhocoricin . European Journal of Biochemistry . 269 . 17 . 4226–37 . September 2002 . 12199701 . 10.1046/j.1432-1033.2002.03119.x . free .
4. Rahnamaeian M, Cytryńska M, Zdybicka-Barabas A, Dobslaff K, Wiesner J, Twyman RM, Zuchner T, Sadd BM, Regoes RR, Schmid-Hempel P, Vilcinskas A . Insect antimicrobial peptides show potentiating functional interactions against Gram-negative bacteria . Proceedings. Biological Sciences . 282 . 1806 . 20150293 . May 2015 . 25833860 . 4426631 . 10.1098/rspb.2015.0293 .
5. Florin T, Maracci C, Graf M, Karki P, Klepacki D, Berninghausen O, Beckmann R, Vázquez-Laslop N, Wilson DN, Rodnina MV, Mankin AS . An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome . Nature Structural & Molecular Biology . 24 . 9 . 752–757 . September 2017 . 28741611 . 5589491 . 10.1038/nsmb.3439 .
6. Narayanan S, Modak JK, Ryan CS, Garcia-Bustos J, Davies JK, Roujeinikova A . Mechanism of Escherichia coli resistance to Pyrrhocoricin . Antimicrobial Agents and Chemotherapy . 58 . 5 . 2754–62 . May 2014 . 24590485 . 3993218 . 10.1128/AAC.02565-13 .