Anthrax lethal factor endopeptidase

An enzyme component of the anthrax toxin that disrupts cellular signaling pathways

Anthrax lethal factor endopeptidase is a zinc metalloprotease enzyme that is a key component of the anthrax toxin, produced by the bacterium Bacillus anthracis. This enzyme plays a crucial role in the pathogenicity of anthrax by disrupting cellular signaling pathways, leading to cell death and contributing to the virulence of the bacterium.

Structure and Function

The anthrax lethal factor endopeptidase is part of the tripartite anthrax toxin, which also includes the protective antigen and the edema factor. The lethal factor is a 90 kDa protein that specifically cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family. This cleavage disrupts the MAPK signaling pathway, which is essential for cell growth, differentiation, and survival.

The enzyme is a zinc-dependent protease, meaning it requires a zinc ion in its active site to catalyze the hydrolysis of peptide bonds. The lethal factor specifically targets the N-terminus of MAPKKs, leading to their inactivation.

Mechanism of Action

Once the protective antigen binds to the host cell surface, it facilitates the entry of the lethal factor into the cytosol. Inside the cell, the lethal factor exerts its toxic effects by cleaving MAPKKs, thereby inhibiting the MAPK signaling cascade. This inhibition leads to apoptosis (programmed cell death) and immune system evasion, allowing Bacillus anthracis to proliferate and cause disease.

Clinical Significance

The anthrax lethal factor endopeptidase is a major virulence factor of Bacillus anthracis, and its activity is a target for therapeutic intervention. Understanding the structure and function of this enzyme has been crucial in developing potential treatments and vaccines against anthrax.

Research and Therapeutic Development

Research into the anthrax lethal factor has led to the development of inhibitors that can block its protease activity. These inhibitors are being explored as potential therapeutic agents to treat anthrax infections. Additionally, the lethal factor is a target for vaccine development, aiming to elicit an immune response that neutralizes its activity.

Also see

• Anthrax
• Bacillus anthracis
• Protective antigen
• Edema factor
• Zinc metalloprotease
• Mitogen-activated protein kinase