Structural features of a superfamily of zinc-endopeptidases: the metzincins

Abstract

A large number of zinc endopeptidases contain an HEXXHXXGXXH consensus motif in their catalytic site (single letter code; X is any amino acid residue). These enzymes can be grouped into four distinct families, the astacins, the adamalysins, the serralysins and the matrix metalloproteinases (matrixins). Despite a low degree of sequence similarity, their catalytic modules are topologically similar. A topology derived sequence alignment suggests that the four families form a superfamily, called the metzincins because of a perfectly superimposable methionine residue close to the zinc-binding active site. Topological similarity to the thermolysin-like enzymes indicates that these enzymes may have had a common ancestor.