Mdluli K, Slayden R A, Zhu Y, Ramaswamy S, Pan X, Mead D, Crane D D, Musser J M, Barry C E
Tuberculosis Research Unit, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases (NIAID), National Institutes of Health, Hamilton, MT 59840, USA.
Science. 1998 Jun 5;280(5369):1607-10. doi: 10.1126/science.280.5369.1607.
Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta-ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug.
尽管异烟肼（异烟酸酰肼，INH）被广泛用于治疗结核病，但其分子靶点一直难以捉摸。在异烟肼治疗反应中，饱和二十六烷酸（C26:0）在一个12千道尔顿的酰基载体蛋白（AcpM）上积累，该蛋白通常携带长达C50的分枝菌酸前体。从经异烟肼处理的结核分枝杆菌中纯化出的一种蛋白质被证明是由异烟肼、AcpM和一种β-酮酰基酰基载体蛋白合酶KasA组成的共价复合物。在耐异烟肼的患者分离株中鉴定出KasA蛋白中的氨基酸改变突变，这些分离株缺乏与该药物耐药性相关的其他突变。
