CLINICAL IMPORTANCE OF METALLOPROTEINASES AND THEIR INHIBITORS
CLINICAL IMPORTANCE OF METALLOPROTEINASES AND THEIR INHIBITORS
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DOI：
10.1111/j.1749-6632.1994.tb24719.x
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发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
KRANE, SM
中科院分区：
文献类型：
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作者：
KRANE, SM
结缔组织的完整性取决于其细胞外基质（ECM）成分的吸收和修复的平衡。蛋白水解酶的活性是降解的速率限制，因此是胶原蛋白和 ECM 的其他大分子成分的吸收的速率限制。”因此，MMP 基因是这些炎症和恶性病变中细胞表达最丰富的基因之一，这一点非常令人感兴趣。基质金属蛋白酶 (MMP) 或基质蛋白是一个大的蛋白酶亚家族的成员，该亚家族包含紧密结合的锌。更大的超家族的其他相关亚家族成员包括嗜热菌蛋白酶、虾红素以及沙雷氏菌和蛇毒金属蛋白酶。是所有这些酶中的催化锌结合结构域，包括序列基序 HEXXH，其中 Glu (E) 充当催化碱基 MMP 的基质蛋白亚家族包含至少 12 个成员，每个成员都是不同基因的产物 3.4, 9 基因亚家族中包括编码至少两种间质胶原酶、三种基质溶解素和几种明胶酶的基因。包含“半胱氨酸开关”的前肽结构域、l0J1 具有序列 HEXGHXXGXXHS 的催化锌结合结构域和血红素样 d~ main。~,~
The integrity of connective tissues is determined by the balance of resorption and repair of components of their extracellular matrix (ECM). The activity of proteolytic enzymes is rate-limiting for the degradation and therefore the resorption of the collagen and other macromolecular constituents of the ECM.’“There is considerable evidence that, among potential proteinases, the matrix metalloproteinases (MMPs) have a major role in physiological resorption of collagen and other macromolecules in development and postnatal remodeling and in pathological resorption associated, for example, with local invasiveness of malignant tumors, resorption of the periodontal structures in periodontal disease, and the destruction of joints in rheumatoid arthritis7 It is thus of considerable interest that the MMP genes are among the most abundant of those expressed by cells in these inflammatory and malignant lesions.The matrix metalloproteinases (MMPs) or matrixins are members of a large subfamily of proteinases that contain tightly bound zinc. Other related subfamily members of an even larger superfamily include thermolysin, astacin, and the serratia and snake venom metalloproteinases. There is a catalytic zinc-binding domain in all of these enzymes that includes a sequence motif HEXXH in which the Glu (E) acts as a catalytic base. The matrixin subfamily of MMPs comprises at least twelve members, each of which is the product of a different gene. 3.4, 9 Included in the gene subfamily are those that encode at least two interstitial collagenases, three stromelysins, and several gelatinases. The matrixins have several structural features in common that include a propeptide domain that contains the “cysteine switch,” l0J1 the catalytic zinc-binding domain with the sequence HEXGHXXGXXHS, and a hemopexin-like d~ main.~,~