Lipoate-protein ligase B (LipB)

Lipoate-protein ligase B (LipB) is an essential enzyme in many bacteria, including Mycobacterium tuberculosis, responsible for the first step of the de novo lipoylation pathway (UniProt P9WKI3). It functions as an octanoyltransferase, transferring an octanoyl group from octanoyl-acyl carrier protein (ACP) to the epsilon-amino group of a specific lysine residue on lipoyl-dependent enzymes, such as the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes (PubMed: 21903593). These complexes are vital for aerobic metabolism and energy production. Because humans utilize a different pathway for lipoylation, LipB represents a promising target for the development of narrow-spectrum antibacterial agents (PubMed: 25105314). Inhibition of LipB leads to the loss of function of these key metabolic enzymes, ultimately resulting in bacterial growth arrest or death. Current research focuses on small molecule inhibitors that mimic the transition state of the octanoyl transfer reaction to treat drug-resistant infections (PubChem CID 118705605).

Other names

LipoyltransferaseOctanoyltransferaseOctanoyl-[acyl-carrier-protein]--protein N-octanoyltransferaseLipoate-protein ligase B

Inhibition of octanoyltransferase activity, preventing the lipoylation and subsequent activation of essential 2-oxoacid dehydrogenase complexes.