The metalloproteinase of Leishmania: leishmanolysin

ABSTRACT

Zinc metalloproteinases are a diverse group of endo- and exoproteinases related only by their common catalytic mechanism and similar primary structure defining the metal binding domain. They are involved in tissue remodelling, metastasis, peptide hormone processing and digestion. Outside of the zinc binding site, their primary structures are highly divergent, suggesting that this group of enzymes is the product of convergent evolution. The three dimensional structures of small soluble bacterial (thermolysin) and eukaryote (astacin) metalloproteinases has allowed the establishment of several families of metalloproteinases based upon the zinc binding ligands of the enzymes. Thus far, no high-molecular weight membrane bound metalloproteinase has been crystallised; unfortunately these are among the most interesting in terms of human physiology. Leishmanolysin, the abundant surface metalloproteinase of several genera of kinetoplastid protozoans, most notably Leishmania, provides an abundant source of glycophosphatidylinositol-anchored glycoprotein for biochemical and structural studies, which will not only lead to a better understanding of the role of the proteinase in the life cycle of the protozoan, but will also provide a framework upon which to model the structures of mammalian metalloproteinases.