Ren J, Bretthauer R K, Castellino F J
Department of Chemistry and Biochemistry, University of Notre Dame, Indiana 46556.
Biochemistry. 1995 Feb 28;34(8):2489-95. doi: 10.1021/bi00008a012.
Because the availability and subcellular distribution of processing mannosidases in cells play such powerful roles in determining ultimate structures of glycoconjugates, we desired to identify, characterize, and investigate possible regulation of mannosidases in infected and noninfected lepidopteran insect cells. Since our previous observations that a mannosidase activity that converted Man6GlcNAc2 to Man5GlcNAc2 was enhanced in virus-infected cells, thus providing the necessary intermediate for further processing to complex-type oligosaccharides, we attempted purification of this enzyme. A mannosidase was isolated and purified from membranes, operationally defined as Golgi, of recombinant baculovirus-infected Spodoptera frugiperda (IPLB-SF-21AE) cells. The molecular mass of this protein was approximately 63 kDa. Assays performed by measuring the conversion of NaB3H4-reduced Man6GlcNAc2-ol to Man5GlcNAc-[3H]GlcNAc2-ol demonstrated that the mannosidase activity was dependent on the presence of divalent cations, which was optimal for Ca2+ at pH 6.0. Inclusion of 1-deoxymannojirimycin resulted in 50% inhibition at a concentration of 20 microM, whereas swainsonine did not show such inhibition. No activity was observed with p-nitrophenyl alpha-D-mannoside (4 mM) as a substrate. The preferred reduced oligosaccharide substrate was Man6GlcNAc2-ol, with lower activities obtained with Man9GlcNAc2-ol, Man8GlcNAc2-ol, and Man7GlcNAc2-ol. With Man6GlcNAc2-ol as substrate, products smaller than reduced Man5GlcNAc2-ol were not observed. Mannose was also liberated from the glycoprotein, ovalbumin. These properties are consistent with an enzyme classification as a type I (alpha 1,2)-Man6-mannosidase.
由于细胞中加工甘露糖苷酶的可用性和亚细胞分布在决定糖缀合物的最终结构中发挥着如此重要的作用,我们希望鉴定、表征并研究感染和未感染的鳞翅目昆虫细胞中甘露糖苷酶的可能调控。基于我们之前的观察,即病毒感染的细胞中一种将Man6GlcNAc2转化为Man5GlcNAc2的甘露糖苷酶活性增强,从而为进一步加工成复杂型寡糖提供了必要的中间体,我们尝试纯化这种酶。从重组杆状病毒感染的草地贪夜蛾(IPLB - SF - 21AE)细胞的膜(操作上定义为高尔基体)中分离并纯化了一种甘露糖苷酶。这种蛋白质的分子量约为63 kDa。通过测量NaB3H4还原的Man6GlcNAc2 - ol向Man5GlcNAc - [3H]GlcNAc2 - ol的转化进行的测定表明,甘露糖苷酶活性依赖于二价阳离子的存在,在pH 6.0时对Ca2 + 最为适宜。加入1 - 脱氧甘露基野尻霉素在浓度为20 microM时导致50%的抑制,而苦马豆素未显示出这种抑制作用。以对硝基苯基α - D - 甘露糖苷(4 mM)作为底物未观察到活性。优选的还原寡糖底物是Man6GlcNAc2 - ol,对于Man9GlcNAc2 - ol、Man8GlcNAc2 - ol和Man7GlcNAc2 - ol获得的活性较低。以Man6GlcNAc2 - ol作为底物时,未观察到比还原的Man5GlcNAc2 - ol更小的产物。甘露糖也从糖蛋白卵清蛋白中释放出来。这些特性与一种被归类为I型(α1,2)- Man6 - 甘露糖苷酶的酶一致。