Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Science. 1999 Jun 4;284(5420):1667-70. doi: 10.1126/science.284.5420.1667.
Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases characterized by abnormal connective tissue turnover. MMPs are expressed as latent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure of proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of loops essential for propeptide stability.
基质金属蛋白酶（MMPs）催化细胞外基质降解。控制其活性是治疗以结缔组织异常更新为特征的疾病的一个有前景的靶点。MMPs以无活性的酶原形式表达，通过蛋白水解切割激活，从而引发前肽（半胱氨酸开关）的构象变化。前MMP-2的结构揭示了前肽如何屏蔽催化裂隙，以及半胱氨酸开关可能通过切割对前肽稳定性至关重要的环来发挥作用。
