结核分枝杆菌异柠檬酸裂解酶通过与 N 端结合被槲皮素抑制。
Isocitrate lyase of Mycobacterium tuberculosis is inhibited by quercetin through binding at N-terminus.
机构信息
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226 031, India.
出版信息
Int J Biol Macromol. 2015;78:137-41. doi: 10.1016/j.ijbiomac.2015.04.005. Epub 2015 Apr 11.
Combating tuberculosis requires new therapeutic strategies that not only target the actively dividing bacilli but also the dormant bacilli during persistent infection. Isocitrate lyase (ICL) is a key enzyme of the glyoxylate shunt, crucial for the survival of bacteria in macrophages and mice. MtbICL is considered as one of the potential and attractive drug targets against persistent infection. We report the inhibition of MtbICL by quercetin with IC50 of 3.57 μM. In addition, quercetin strongly inhibited the growth of Mtb H37Rv utilizing acetate, rather than glucose as the sole carbon source, suggesting the inhibition of glyoxylate shunt. Quercetin binds at the N-terminus of MtbICL (Kd - 6.68 μM).
抗结核需要新的治疗策略，不仅要针对活跃分裂的细菌，还要针对持续感染期间休眠的细菌。异柠檬酸裂解酶（ICL）是乙醛酸支路的关键酶，对细菌在巨噬细胞和小鼠中的存活至关重要。 MtbICL 被认为是针对持续感染的潜在有吸引力的药物靶点之一。我们报告了槲皮素对 MtbICL 的抑制作用，其 IC50 为 3.57 μM。此外，槲皮素强烈抑制了利用醋酸盐而不是葡萄糖作为唯一碳源的 Mtb H37Rv 的生长，表明抑制了乙醛酸支路。槲皮素结合在 MtbICL 的 N 端（Kd - 6.68 μM）。
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