蝶呤型钼辅因子生物合成、运输及组装——潜在的药物靶标

Biosynthesis,Transferer and Assembly of Pterin-based Molybdenum Cofactors: Potential Drug Targets

钼辅因子作为氧化还原反应中的重要分子,参与硫、氮、碳的氧化还原代谢.钼辅因子主要分为两类:以铁硫簇为基础的铁钼辅因子和以亚钼蝶呤为基础的钼辅因子.钼-二-亚钼蝶呤-鸟苷二核苷钼辅因子(Mo-bis-MGD)是蝶呤型钼辅因子的重要成员之一,是硝酸盐还原酶的重要辅因子.膜结合硝酸盐还原酶介导的硝酸盐还原为细菌提供了氮源和能源,与分枝杆菌的持留性感染相关.此外,膜结合硝酸盐还原酶能显著增加卡介苗在免疫缺陷鼠中的毒性.人与细菌中蝶呤型钼辅因子生物合成、运输和组装的差异提示,Mo-bis-MGD型钼辅因子的生物合成途径很可能作为新型药物靶标,有益于抗病原菌,尤其有利于抗多重耐药结核分枝杆菌新药的开发研究.

As a crucial molecule participating in catalyzing reduction-oxidation（redox） reactions,molybdenum cofactors involve in the redox metabolism of sulphur,nitrogen and carbon.Molybdenum cofactors are generally divided into two groups： the iron-sulphur-cluster-based iron-molybdenum cofactor（FeMo-co） and the pterin-based molybdenum cofactor（Moco）.Mo-bis-molybdopterin guanine dinucleotide（Mo-bis-MGD） is one member of Moco,which is important cofactor of nitrate reductase.Membrane-bound nitrate reductase mediating the reduction of nitrate provides bacteria with energy and nitrogen source,which is related with latent tuberculosis infection.Moreover,membrane-bound nitrate reductase contributes significantly to the virulence of Mycobacterium bovis BCG in immunodeficient mice.The difference of biosynthesis,transference and assembly of Moco between human and bacteria indicates that the steps of biosyntheis of Mo-bis-MGD might be developed as novel drug targets to screen novel antibiotics against pathogens,particularly the（multi）drug-resistant Mycobcterium tuberculosis.