The astacin family of metalloendopeptidases.
Molecular cloning of a human intestinal brush border metalloendopeptidase (N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase, PPH) and a mouse kidney brush border metalloendopeptidase (meprin A) has revealed 82% identity in the NH2-terminal amino acid sequences (198 residues) of the mature enzymes. Furthermore, searching of protein sequence data bases with the inferred peptide sequences as probes revealed strong similarities to astacin, a crayfish digestive protease, and an NH2-terminal domain of a human bone morphogenetic protein (BMP-1). Meprin A and PPH both have approximately 30% identity with astacin and BMP-1. Multiple alignment analysis indicated that 37 residues, including 3 cysteine residues, are strictly conserved for the four proteins in a sequence frame equivalent to the complete 200-amino acid astacin sequence. The four proteins contain a zinc-binding motif (HEXXH), found at the active site of most metalloendopeptidases, within an extended sequence of HEXXHXXGFXHE which is unique to this subgroup of metalloendopeptidases. In addition, the four proteins have 54% identity in a 24-amino acid sequence that includes the putative active site. A fifth protein, Xenopus laevis developmentally regulated protein UVS.2, also shares sequence identity with the metalloendopeptidases. These data provide strong evidence for an evolutionary relationship of these proteins. It is suggested that this new family of metalloendopeptidases be called the "astacin family."
Dumermuth
E
E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Berne, Switzerland.
Sterchi
E E
EE
Jiang
W P
WP
Wolz
R L
RL
Bond
J S
JS
Flannery
A V
AV
Beynon
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006801:Humans; D007422:Intestines / Q000201:enzymology; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D008871:Microvilli / Q000201:enzymology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
D009838:Oligodeoxyribonucleotides; D008666:Metalloendopeptidases; C071288:astacin