3krd

Structural highlights

Function

[PSA_MYCTU] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages, since the core proteasome is essential for persistence of the pathogen during the chronic phase of infection in mice. The mechanism of protection against bactericidal chemistries of the host's immune response probably involves the degradation of proteins that are irreversibly oxidized, nitrated, or nitrosated.^{[1] [2]} [PSB_MYCTU] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages, since the core proteasome is essential for persistence of the pathogen during the chronic phase of infection in mice. The mechanism of protection against bactericidal chemistries of the host's immune response probably involves the degradation of proteins that are irreversibly oxidized, nitrated, or nitrosated.^{[3] [4]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Jmol/Visualizing large molecules
• Proteasome

References

1. ↑ Lin G, Hu G, Tsu C, Kunes YZ, Li H, Dick L, Parsons T, Li P, Chen Z, Zwickl P, Weich N, Nathan C. Mycobacterium tuberculosis prcBA genes encode a gated proteasome with broad oligopeptide specificity. Mol Microbiol. 2006 Mar;59(5):1405-16. PMID:16468985 doi:http://dx.doi.org/10.1111/j.1365-2958.2005.05035.x
2. ↑ Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S. In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nat Med. 2007 Dec;13(12):1515-20. Epub 2007 Dec 2. PMID:18059281 doi:http://dx.doi.org/10.1038/nm1683
3. ↑ Lin G, Hu G, Tsu C, Kunes YZ, Li H, Dick L, Parsons T, Li P, Chen Z, Zwickl P, Weich N, Nathan C. Mycobacterium tuberculosis prcBA genes encode a gated proteasome with broad oligopeptide specificity. Mol Microbiol. 2006 Mar;59(5):1405-16. PMID:16468985 doi:http://dx.doi.org/10.1111/j.1365-2958.2005.05035.x
4. ↑ Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S. In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nat Med. 2007 Dec;13(12):1515-20. Epub 2007 Dec 2. PMID:18059281 doi:http://dx.doi.org/10.1038/nm1683
5. ↑ Lin G, Li D, Chidawanyika T, Nathan C, Li H. Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome. Arch Biochem Biophys. 2010 Sep 15;501(2):214-20. Epub 2010 Jun 15. PMID:20558127 doi:10.1016/j.abb.2010.06.009