Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus aztecus.
A new antimicrobial peptide, hadrurin, was isolated from the venom of the Mexican scorpion Hadrurus aztecus, by gel filtration on a Sephadex G-50 column, followed by high performance liquid chromatography. It is a basic peptide composed of 41 amino-acid residues with a molecular mass of 4436 Da, and contains no cysteines. A model of the three-dimensional folding of hadrurin is compatible with that of an amphipatic molecule with two alpha-helical segments. Hadrurin demonstrates antimicrobial activity at low micromolar concentration, inhibiting the growth of bacteria such as: Salmonella thyphi, Klebsiella pneumoniae, Enterococcus cloacae, Pseudomonas aeruginosa, Escherichia coli and Serratia marscences. It also shows cytolytic activity when tested in human erythrocytes. Hadrurin and two analogs (C-terminal amidated, and all D-enantiomer) were chemically synthesized. They were used to study the possible molecular mechanism of action by testing their ability to dissipate the diffusion potential of liposomes of different compositions. The results obtained indicate that there are no specific receptor molecules for the action of hadrurin, and the most probable mechanism is through a membrane destabilization activity. It is surmised that hadrurin is used by the scorpion as both an attack and defense element against its prey and putative invasive microorganisms. It is a unique peptide among all known antimicrobial peptides described, only partially similar to the N-terminal segment of gaegurin 4 and brevinin 2e, isolated from frog skin. It would certainly be a model molecule for studying new antibiotic activities and peptide-lipid interactions.
Torres-Larios
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A
Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, Avenida Universidad, Cuernavaca, Mexico.
Gurrola
G B
GB
Zamudio
F Z
FZ
Possani
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D016983:Enterococcus / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008800:Mexico; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012485:Salmonella typhi / Q000187:drug effects; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D012605:Scorpions; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012706:Serratia marcescens / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D012604:Scorpion Venoms; C414302:hadrurin