Effects of detergents on catalytic activity of human endometase/matrilysin 2, a putative cancer biomarker.
Effects of detergents on catalytic activity of human endometase/matrilysin 2, a putative cancer biomarker.
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去污剂对人内转移酶/基质溶素 2（一种假定的癌症生物标志物）催化活性的影响。
DOI：
10.1016/j.ab.2009.10.005
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发表时间：
2010
影响因子：
2.9
通讯作者：
Sang,Qing-XiangAmy
中科院分区：
文献类型：
--
作者：
Park,HyunI;Lee,Seakwoo;Ullah,Asad;Cao,Qiang;Sang,Qing-XiangAmy
基质金属蛋白酶 (MMP) 是一个水解酶家族，在发育、形态发生、炎症和癌症侵袭中发挥重要作用。 Endometase（基质溶素 2 或 MMP-26）是人类癌症的推定早期生物标志物。研究了离子型和非离子型去垢剂对内梅酶催化活性的影响。内梅酶的水解活性与去污剂浓度相关，表现出钟形曲线，其最大活性接近测试的非离子去污剂的临界胶束浓度（CMC）。进一步探讨了 Brij-35 对人明胶酶 B (MMP-9)、基质溶解素 (MMP-7) 和膜型 1 MMP (MT1-MMP) 的影响。在 Brij-35 (∼ 90μM) 的 CMC 附近观察到它们的最大催化作用。它们的 IC50 值高于 CMC。根据Dixon图确定Brij-35对MMP-7、MMP-9和MT1-MMP的抑制机制为混合型；然而，内皮酶的抑制机制是非竞争性的，Ki值为240μM。 MMP 的催化活性受去污剂的影响。去垢剂的单体可以激活和稳定MMP以增强催化作用，但去垢剂的胶束可能会螯合酶并阻断底物结合位点以阻碍催化作用。在生理条件下，脂质或膜微环境可以调节酶活性。
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90μM). Their IC50values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a Kivalue of 240μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity.