Rozwarski D A, Grant G A, Barton D H, Jacobs W R, Sacchettini J C
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Science. 1998 Jan 2;279(5347):98-102. doi: 10.1126/science.279.5347.98.
The preferred antitubercular drug isoniazid specifically targets a long-chain enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Despite the widespread use of this drug for more than 40 years, its precise mode of action has remained obscure. Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of InhA.
首选的抗结核药物异烟肼专门作用于一种长链烯酰-酰基载体蛋白还原酶（InhA），该酶是结核分枝杆菌中分枝菌酸生物合成所必需的。尽管这种药物已广泛使用40多年，但其确切作用方式仍不清楚。X射线晶体学和质谱数据表明，异烟肼对InhA的作用机制是药物的活化形式与结合在InhA活性位点内的烟酰胺腺嘌呤二核苷酸的烟酰胺环发生共价连接。
