MATRIX METALLOPROTEINASES - STRUCTURES, EVOLUTION, AND DIVERSIFICATION

A comprehensive sequence alignment of 64 members of the family of matr ix metalloproteinases (MMPs) for the entire sequences, and subsequentl y the catalytic and the hemopexin-like domains, have been performed. T he 64 MMPs were selected from plants, invertebrates, and vertebrates. The analyses disclosed that as many as 23 distinct subfamilies of thes e proteins are known to exist. Information from the sequence alignment s: was correlated with structures, both crystallographic as well as co mputational, of the catalytic domains for the 23 representative member s of the MMP family. A survey of the metal binding sites and two loops containing variable sequences of amino acids, which are important for substrate interactions, are discussed. The collective data support th e proposal that the assembly of the domains into multidomain enzymes w as likely to be an early evolutionary event. This:was followed by dive rsification, perhaps in parallel among the MMPs, in a subsequent evolu tionary time scale. Analysis indicates that a retrograde structure sim plification may have accounted for the evolution of MMPs with simple d omain constituents, such as matrilysin, from the larger and more elabo rate enzymes.