Mycobacterium tuberculosis 20S proteasome beta subunit (PrcB)

The Mycobacterium tuberculosis 20S proteasome beta subunit (PrcB) is the catalytic component of the 20S core particle, an energy-dependent protease complex essential for the pathogen's survival and persistence within the host [UniProt: P9WIA9]. Unlike the multi-subunit eukaryotic proteasome, the Mtb 20S proteasome is a simpler assembly of 14 alpha (PrcA) and 14 beta (PrcB) subunits, with the beta subunits housing the N-terminal threonine active sites [PubMed: 12524535]. This target is particularly crucial for Mtb to withstand nitrosative stress encountered inside host macrophages, as it degrades proteins damaged by reactive nitrogen species [Nature 2003, 422(6929):317-20]. Inhibition of PrcB leads to the accumulation of pupylated proteins and lethal proteotoxic stress, making it a validated target for anti-tubercular drug discovery. Current research focuses on developing selective inhibitors, such as oxathiazol-2-ones and N,C-capped dipeptides, that specifically target the Mtb proteasome while sparing the human counterpart to minimize host toxicity [Nature 2009, 461(7264):621-6]. By disrupting protein homeostasis, these inhibitors can kill both actively replicating and dormant mycobacteria, offering a potential pathway to shorten tuberculosis treatment duration.

Other names

Proteasome subunit betaPrcBRv211020S core particle beta subunitThreonine protease PrcBMycobacterium tuberculosis 20S proteasome beta subunit

Covalent or non-covalent inhibition of the catalytic N-terminal threonine residue of the beta subunit, blocking the proteolytic activity of the 20S proteasome core [Nature 2009].