Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc‐binding environments (HEXXHXXGXXH and Met‐turn) and topologies and should be grouped into a common family, the ‘metzincins’

Abstract

The X-ray crystal structures of two zmc endopeptldases. astacin from crayfish. and adamalysm II from snake venom, reveal a strong overall lopologlcal equivalence and virtually Identical extended HEXXHXXGXXH zinc-binding segments, but m addition a methlomne-containing turn of similar conformatlon (the 'Met-turn'). which forms a hydrophobic basis for the zmc ion and the three ligandmg hlstidine residues. These two features are also present in a similar arrangement m the matrix metalloproteinases (matrixins) and in the large bacterial Serratra proteinase-like peptidases (serralysins).We suggest that these four proteinases represent members of distinct subfamilies which can be grouped together in a family, for which we propose the designation, metzmcins.Astacm; Snake venom metalloproteinase; Matrix metalloprotemase; Thermolysm; Zmc endopeptidase family: Protein crystal structure

Matrix metalloproteinases and the regulation of tissue remodelling

“…MMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 in which MMPs include the M10A subfamily, the M10 family and the MA clan of metallopeptidases.…”

The astacin family of metalloendopeptidases

“…2) in zinc binding and the methionine involved in a "Met-turn" of the peptide chain Bode et al, 1993;Stocker et al, 1995). Stocker and colleagues (1993) identified other specific residues that are conserved, in comparisons of 10 members of the astacin family, and are probably crucial to the overall structure of the protease domain.…”

Cloning and characterization of ADAM28: evidence for autocatalytic pro-domain removal and for cell surface localization of mature ADAM28

“…In (B) and (C), total RNA from mouse lung or epididymis (25 µg/lane) was probed with (B) a 32 Plabelled cDNA probe corresponding to ADAM28 bases 1246-1613 (encoding a portion of the metalloprotease and disintegrin-like domains), or (C) a 32 Like other metalloprotease disintegrins, mouse ADAM28 consists of several domains : a signal sequence followed by a prodomain, a metalloprotease domain, a disintegrin-like domain, a cysteine-rich region, an EGF-like repeat, a membrane-spanning sequence and a cytoplasmic tail (Figure 1). ADAM28 possesses a catalytic zinc-binding consensus sequence (His-Glu-Xaa-XaaHis ; HEXXH) followed by a Met-turn, a characteristic feature of metalloproteases belonging to the metzincin family [5,6]. These features suggest that ADAM28 is a catalytically active metalloprotease.…”

“…In most cases these proteins also include an epidermal growth factor (EGF) repeat, a transmembrane domain and a cytoplasmic tail. Of the 30 currently known ADAMs, 17 are predicted to be catalytically active, because they carry a catalytic site consensus sequence (HEXXH) followed by a Met-turn, a characteristic feature of the metzincin family of metalloproteases [5,6]. The remaining 13 ADAMs lack a zinc-binding catalytic site and are not predicted to be catalytically active, even though the sequence of the metalloprotease domain is otherwise clearly conserved [three frequently updated websites provide access to the GenBank accession numbers and sequence alignments of known ADAMs : (1) www.people.Virginia.EDU\"jag6n\ adams.html ; (2) www.uta.fi\"loiika\HADAMs.html ; and (3) www.gene.ucl.ac.uk\users\hester\metallo.html].…”