Bhattacharyya Rajasri, Banerjee Dibyajyoti
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India.
Bioinformation. 2011;7(7):324-7. doi: 10.6026/97320630007324. Epub 2011 Dec 10.
Tuberculosis is known to occur more in cases of chronic diabetes mellitus. The exact cause of such an association is mostly unknown. Recently we have shown using tools of computational biology that glycation of the subunits of respiratory burst enzyme NADPH oxidase may impair intra-macrophage killing of Mycobacterium tuberculosis. Since glycation of proteins including subunits of NADPH oxidase will be significantly increased in long standing uncontrolled diabetes we have concluded that it may be an important factor for increased association of tuberculosis in diabetic state. Analogous to NADPH oxidase, role of NOS is proved beyond any doubt for killing of intracellular pathogen like Mycobacterium tuberculosis. Based on the above mentioned premises, in this work we have studied glycation of various domains of iNOS using tools of computational biology and observed that glycation of K531 of Calmodulin binding domain of iNOS may impair the enzyme activity. We have concluded that the above phenomenon can happen at chronic diabetic state which may render the host susceptible to tuberculosis.
众所周知，结核病在慢性糖尿病患者中更为常见。这种关联的确切原因大多未知。最近，我们利用计算生物学工具表明，呼吸爆发酶NADPH氧化酶亚基的糖基化可能会损害巨噬细胞内对结核分枝杆菌的杀伤作用。由于包括NADPH氧化酶亚基在内的蛋白质糖基化在长期未控制的糖尿病中会显著增加，我们得出结论，这可能是糖尿病状态下结核病关联增加的一个重要因素。与NADPH氧化酶类似，一氧化氮合酶（NOS）在杀灭细胞内病原体如结核分枝杆菌方面的作用已毫无疑问地得到证实。基于上述前提，在这项工作中，我们利用计算生物学工具研究了诱导型一氧化氮合酶（iNOS）各个结构域的糖基化情况，并观察到iNOS钙调蛋白结合结构域的K531糖基化可能会损害酶活性。我们得出结论，上述现象可能发生在慢性糖尿病状态，这可能使宿主易患结核病。
