Catalytic domain architecture of metzincin metalloproteases.
Metalloproteases cleave proteins and peptides, and deregulation of their function leads to pathology. An understanding of their structure and mechanisms of action is necessary to the development of strategies for their regulation. Among metallopeptidases are the metzincins, which are mostly multidomain proteins with approximately 130-260-residue globular catalytic domains showing a common core architecture characterized by a long zinc-binding consensus motif, HEXXHXXGXX(H/D), and a methionine-containing Met-turn. Metzincins participate in unspecific protein degradation such as digestion of intake proteins and tissue development, maintenance, and remodeling, but they are also involved in highly specific cleavage events to activate or inactivate themselves or other (pro)enzymes and bioactive peptides. Metzincins are subdivided into families, and seven such families have been analyzed at the structural level: the astacins, ADAMs/adamalysins/reprolysins, serralysins, matrix metalloproteinases, snapalysins, leishmanolysins, and pappalysins. These families are reviewed from a structural point of view.
Gomis-Rüth
F Xavier
FX
Proteolysis Lab, Molecular Biology Institute of Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona Science Park, Helix Building, c/Baldiri Reixac, 15-21, E-08028 Barcelona, Spain. fxgr@ibmb.csic.es
D000818:Animals; D001665:Binding Sites; D016384:Consensus Sequence; D007891:Leishmania / Q000201:enzymology; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism
D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania; D015032:Zinc