A novel endopeptidase from Xenopus that recognizes alpha-helical secondary structure.
The magainin peptides of Xenopus laevis are broad-spectrum antimicrobial agents. Upon discharge from the skin glands, these basic, amphipathic peptides are each further processed at a single Xaa-Lys bond into half-peptides by a cosecreted protease. We describe the characterization and purification to homogeneity of this endopeptidase from Xenopus skin. The enzyme is a metalloprotease 110 kd in size. Analyses of substrate specificity revealed that the endopeptidase recognizes peptides that share the ability to adopt an amphipathic, alpha-helical motif composed of at least 12 residues, with one face strongly hydrophobic. Cleavage occurs on the amino side of a specific lysine that must be precisely positioned relative to the hydrophobic face of the alpha helix. This enzyme, which we propose to call "magaininase," represents a novel class of endopeptidases that hydrolyzes peptides on the basis of specific secondary structure rather than primary amino acid sequence.
Resnick
N M
NM
Division of Human Genetics Children's Hospital of Philadelphia, Pennsylvania.
Maloy
W L
WL
Guy
H R
HR
Zasloff
M
M
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D054806:Magainins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D054806:Magainins; D010455:Peptides; D011480:Protease Inhibitors; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C053300:magainin 1 peptide, Xenopus; D010450:Endopeptidases