N-arginine dibasic convertase, a metalloendopeptidase as a prototype of a class of processing enzymes.
N-Arg dibasic convertase is a metalloendopeptidase from rat brain cortex and testis that cleaves peptide substrates on the N terminus of Arg residues in dibasic stretches. By using both an oligonucleotide and antibodies to screen a rat testis cDNA library, a full-length cDNA was isolated. The sequence contains an open reading frame of 1161 codons corresponding to a protein of 133 kDa that exhibits 35% and 48% similarity with Escherichia coli protease III (pitrilysin, EC 3.4.99.44) and rat or human insulinase (EC 3.4.99.45), respectively. Moreover, the presence of the HXXEH amino acid signature (XX = FL) clearly classifies N-Arg dibasic convertase as a member of the pitrilysin family of zinc-metalloendopeptidases. In addition, a Cys residue that may be responsible for the thiol sensitivity of the insulinase and N-Arg dibasic convertase was proposed. The protein sequence contains a distinctive additional feature consisting of a stretch of 71 acidic amino acids. We hypothesize that this metalloendopeptidase may be a member of a distinct class of processing enzymes.
Pierotti
A R
AR
Université Pierre et Marie Curie, Unité de Recherches Associée au Centre National de la Recherche Scientifique, Paris, France.
Prat
A
A
Chesneau
V
V
Gaudoux
F
F
Leseney
A M
AM
Foulon
T
T
Cohen
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002540:Cerebral Cortex / Q000201:enzymology*; D017124:Conserved Sequence; D010450:Endopeptidases / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D015723:Gene Library; D017403:In Situ Hybridization; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009876:Operon; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000201:enzymology*
D009838:Oligodeoxyribonucleotides; D010450:Endopeptidases; D008666:Metalloendopeptidases; C046583:pitrilysin; C087976:nardilysin