That impish TIMP: the tissue inhibitor of metalloproteinases-3.
That impish TIMP: the tissue inhibitor of metalloproteinases-3.
复制标题
TIMP 是一种顽皮的东西：金属蛋白酶 3 的组织抑制剂。
DOI：
10.1172/jci13709
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
J. Woessner
中科院分区：
文献类型：
--
作者：
J. Woessner
不受限制的消化不会破坏关键组织。大多数MMPs仅在需要时以低水平产生;它们作为酶原分泌，其中前肽的半胱氨酸残基与活性位点锌结合并使其失活。最重要的是，有一组五种TIMP（金属蛋白酶的组织抑制剂），每种都能够抑制MMP家族的几乎每一个成员。TIMP是约21，000 Da的小蛋白，含有两个结构域：N-末端和C-末端。每个结构域含有三个二硫键，使TIMP相当稳定。迄今为止发现的大多数生物学功能位于约125个残基的N-末端结构域中（5）。通常，TIMP与MMP处于微妙的平衡，并且基质以高度调节的方式被消化。然而，存在许多疾病过程，其中MMP水平升高而没有伴随的TIMP增加，导致失衡和由此产生的组织破坏。一些众所周知的例子包括骨关节炎和类风湿性关节炎中软骨基质的丢失，动脉粥样硬化中斑块帽的破裂，以及肿瘤细胞的侵袭和转移（6）。TIMPs的一个令人惊讶的特征是
untrammeled digestion does not destroy critical tissues. Most MMPs are made only upon demand and in low levels; they are secreted as proenzymes in which a cysteine residue of the propeptide binds to and inactivates the active-site zinc. Most importantly, there is a group of five TIMPs (tissue inhibitors of metalloproteinases) that are each capable of inhibiting almost every member of the MMP family. The TIMPs are small proteins of about 21,000 Da that contain two domains: N-terminal and C-terminal. Each domain contains three disulfide bridges, making the TIMPs quite stable. Most of the biological functions discovered so far reside in the N-terminal domain of about 125 residues (5). Normally, the TIMPs are in delicate balance with the MMPs and matrix is digested in a highly regulated fashion. However, there are many disease processes in which MMP levels are elevated without a concomitant increase in TIMPs, leading to an imbalance and the resultant destruction of tissues. Some wellknown examples include the loss of cartilage matrix in osteo- and rheumatoid arthritis, the rupture of the plaque cap in atherosclerosis, and the invasion and metastasis of tumor cells (6). A surprising feature of the TIMPs is