(3R)-hydroxyacyl-ACP dehydratase complex (HadABC) (HadABC)

The (3R)-hydroxyacyl-ACP dehydratase complex (HadABC) is an essential enzyme system in Mycobacterium tuberculosis that plays a pivotal role in the Fatty Acid Synthase II (FAS-II) pathway (Sacco et al., 2007, PubMed: 17911131). This complex is responsible for the dehydration of (3R)-hydroxyacyl-acyl carrier protein (ACP) to trans-2-enoyl-ACP, a key step in the elongation of long-chain fatty acids that eventually form mycolic acids (Grzegorzewicz et al., 2012, PubMed: 22547444). Mycolic acids are indispensable components of the mycobacterial cell envelope, providing a thick, waxy barrier that protects the pathogen from host immune responses and antibiotics. The complex consists of three proteins—HadA, HadB, and HadC—which organize into functional heterodimers (HadAB and HadBC) to process different chain lengths of fatty acid substrates (UniProt: P9WNG1, P9WNG3, P9WNG5). Due to its essentiality and lack of a human homolog, the (3R)-hydroxyacyl-ACP dehydratase complex is a highly attractive target for the development of new anti-tuberculosis therapies. Drugs such as Isoxyl (Thiocarlide) and Thiacetazone specifically target this complex, leading to the inhibition of cell wall assembly and subsequent bacterial lysis (Brown et al., 2007, PubMed: 17449611).

Other names

HadABC dehydratase complexHadAB complexHadBC complexBeta-hydroxyacyl-ACP dehydrataseFAS-II dehydratase(3R)-hydroxyacyl-ACP dehydratase

Inhibition of the (3R)-hydroxyacyl-ACP dehydratase activity within the FAS-II system, preventing the elongation of fatty acids required for mycolic acid synthesis.