Woessner J F
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101.
FASEB J. 1991 May;5(8):2145-54.
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.
基质金属蛋白酶是一组重要的锌酶，在正常胚胎发育、重塑过程以及许多疾病过程（如关节炎、癌症、牙周炎和骨质疏松症）中负责降解细胞外基质成分，如胶原蛋白和蛋白聚糖。定义了一个基质酶家族，该家族至少包含七个成员，其分子量范围从28,000到92,000，并且在基因序列上与胶原酶相关。所有家族成员均以前体酶的形式分泌，激活后会失去约10,000道尔顿的肽段。酶原的潜伏性是由于一个保守的半胱氨酸在活性中心与锌结合。通过物理（离液剂）、化学（次氯酸、汞制剂）和酶促（胰蛋白酶、纤溶酶）处理使半胱氨酸残基与锌分离，从而克服潜伏性。金属蛋白酶的表达可通过多种作用于基因调控元件（特别是AP - 1结合位点）的因子来开启。一个分子量为28,500或更小的蛋白质抑制剂家族以非共价方式强烈且化学计量地结合，以抑制该家族的成员。血清蛋白α2 -巨球蛋白及其相关蛋白也具有很强抑制作用。
