Lethal factor (LF)

Lethal factor (LF) is a secreted bacterial enzyme that forms one of the three components of anthrax toxin, produced by Bacillus anthracis[4][8]. LF is a zinc-dependent metalloprotease with a molecular mass of about 90 kDa, structurally composed of four domains: one mediates binding to protective antigen (PA), which is required for host cell entry, while the other domains create a substrate-binding groove and house the catalytic center[1][2]. Once introduced into host cytosol by PA, LF cleaves and inactivates most MAPKK (MEK) family proteins by cutting within their N-terminal proline-rich regions, leading to disrupted intracellular signaling, immune cell death (especially macrophages), and a general dysregulation of host immune responses[1][2][4][8]. LF, in combination with PA, forms "lethal toxin" (LeTx), and is essential for the pathogenesis and lethality of anthrax infections. LF-specific inhibitors have been developed as research tools, but there are no licensed drugs specifically targeting LF in clinical scenarios[10].

Other names

LFAnthrax lethal factorBacillus anthracis lethal factor

Inhibition of LF enzymatic activity (metalloprotease inhibition)[10]. Blockade of MAPKK cleavage. Preventing LF entry into the host cell cytosol (by interfering with the assembly or translocation with protective antigen)[3][8]