期刊
CURRENT DRUG TARGETS
卷 16, 期 7, 页码 689-699出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389450116666150416115547
关键词
Acetohydroxyacid synthases; AHAS inhibitors; benzoyl esters; branched chain amino acids; imidazolinones; sulfonylureas
资金
- H(S)NC Board, Mumbai, India
On account of the ever increasing resistance of M. tuberculosis strains to orthodox therapy regimens, the task of combating tuberculosis becomes even more challenging. Therefore, there arises a need to isolate new drug targets and subsequently design specific inhibitors for the same. In bacteria, algae, plants and fungi, the synthesis of Branched Chain Amino Acids (BCAAs) is catalyzed by Acetohydroxyacid Synthases (AHAS) group of enzymes. Bacterial AHAS (EC 2.2.1.6) catalyzes the biosynthesis of isoleucine, leucine and valine by utilizing cofactors like Thiamin Diphosphate (ThDP), Flavin Adenine Dinucleotide (FAD) and a divalent metal cation (Usually Mg2+). The anabolic form of the enzyme which is presently under discussion consists of two subunits out of which one is catalytic while the other is regulatory in nature. The product of this enzyme catalyzed reaction is either 2-acetolactate or 2-aceto-2-hydroxybutyrate obtained from self-condensation of pyruvate or condensation of puruvate and 2-ketobutyrate, respectively. These are further converted to the BCAAs by a series of other enzymes. The step catalyzed by AHAS is the first in the entire cascade and hence can be selectively targeted for the inhibition of this pathway. M. tuberculosis AHAS, which is encoded by the ilvB and ilvN operons is structurally related to E. coli AHAS and has a similar function. Therefore, specific drugs belonging to the classes of sulfonylureas, imidazolinones and benzoyl esters can be used as inhibitors of M. tuberculosis AHAS which would consequently deplete the BCAA supply to the bacteria. Thus, efficient bacteriostasis can be achieved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据