Structure and evolutionary aspects of matrix metalloproteinases: a brief overview

The matrix metalloproteinases (MMPs) are zinc dependent endopeptidases known for their ability to cleave one or several extracellular matrix (ECM) constituents, as well as non-matrix proteins. They comprise a large family of proteinases that share common structural and functional elements and are products of different genes. All members of this family contain a signal peptide, a propeptide and a catalytic domain. The catalytic domain contains two zinc ions and at least one calcium ion coordinated to various residues. All MMPs, with the exception matrilysin, have a hemopexin/vitronectin-like domain that is connected to the catalytic domain by a hinge or linker region. The hemopexin-like domain influences tissue inhibitor of metalloproteinases (TIMP) binding, the binding of certain substrates, membrane activation, and some proteolytic activities. It has been proposed that the origin of MMPs could be traced to before the emergence of vertebrates from invertebrates. It appears conceivable that the domain assemblies occurred at an early stage of the diversification of different MMPs and that they progressed through the evolutionary process independent of one another, and perhaps parallel to each other.