Matrix metalloproteinases and their inhibitors in connective tissue remodeling.
Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.
Woessner
J F
JF
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101.
D000595:Amino Acid Sequence; D000828:Animal Population Groups; D000818:Animals; D003238:Connective Tissue / Q000254:growth & development*; D005109:Extracellular Matrix / Q000737:chemistry* / Q000502:physiology; D018093:Gelatinases; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000737:chemistry / Q000502:physiology; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003012:Microbial Collagenase / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000737:chemistry / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases; D015032:Zinc / Q000378:metabolism
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D003012:Microbial Collagenase; D015032:Zinc