8ct4

Structural highlights

Function

DLDH_MYCTU Lipoamide dehydrogenase is an essential component of the alpha-ketoacid dehydrogenase complexes, namely the pyruvate dehydrogenase (PDH) complex, the branched-chain alpha-ketoacid dehydrogenase (BCKADH) complex, and likely also the 2-oxoglutarate dehydrogenase (ODH) complex. Catalyzes the reoxidation of dihydrolipoyl groups which are covalently attached to the lipoate acyltransferase components (E2) of the complexes. Is also able to catalyze the transhydrogenation of NADH and thio-NAD(+) in the absence of D,L-lipoamide, and the NADH-dependent reduction of quinones in vitro.^{[1] [2] [3] [4] [5]} Together with AhpC, AhpD and DlaT, Lpd constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.^{[6] [7] [8] [9] [10]} Appears to be essential for Mtb pathogenesis.^{[11] [12] [13] [14] [15]}

References

1. ↑ Argyrou A, Blanchard JS. Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Biochemistry. 2001 Sep 25;40(38):11353-63. PMID:11560483
2. ↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
3. ↑ Tian J, Bryk R, Shi S, Erdjument-Bromage H, Tempst P, Nathan C. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol Microbiol. 2005 Aug;57(3):859-68. PMID:16045627 doi:http://dx.doi.org/MMI4741
4. ↑ Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C. Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe. 2011 Jan 20;9(1):21-31. doi: 10.1016/j.chom.2010.12.004. PMID:21238944 doi:http://dx.doi.org/10.1016/j.chom.2010.12.004
5. ↑ Rajashankar KR, Bryk R, Kniewel R, Buglino JA, Nathan CF, Lima CD. Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis. J Biol Chem. 2005 Oct 7;280(40):33977-83. Epub 2005 Aug 10. PMID:16093239 doi:10.1074/jbc.M507466200
6. ↑ Argyrou A, Blanchard JS. Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Biochemistry. 2001 Sep 25;40(38):11353-63. PMID:11560483
7. ↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
8. ↑ Tian J, Bryk R, Shi S, Erdjument-Bromage H, Tempst P, Nathan C. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol Microbiol. 2005 Aug;57(3):859-68. PMID:16045627 doi:http://dx.doi.org/MMI4741
9. ↑ Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C. Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe. 2011 Jan 20;9(1):21-31. doi: 10.1016/j.chom.2010.12.004. PMID:21238944 doi:http://dx.doi.org/10.1016/j.chom.2010.12.004
10. ↑ Rajashankar KR, Bryk R, Kniewel R, Buglino JA, Nathan CF, Lima CD. Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis. J Biol Chem. 2005 Oct 7;280(40):33977-83. Epub 2005 Aug 10. PMID:16093239 doi:10.1074/jbc.M507466200
11. ↑ Argyrou A, Blanchard JS. Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Biochemistry. 2001 Sep 25;40(38):11353-63. PMID:11560483
12. ↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
13. ↑ Tian J, Bryk R, Shi S, Erdjument-Bromage H, Tempst P, Nathan C. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol Microbiol. 2005 Aug;57(3):859-68. PMID:16045627 doi:http://dx.doi.org/MMI4741
14. ↑ Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C. Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe. 2011 Jan 20;9(1):21-31. doi: 10.1016/j.chom.2010.12.004. PMID:21238944 doi:http://dx.doi.org/10.1016/j.chom.2010.12.004
15. ↑ Rajashankar KR, Bryk R, Kniewel R, Buglino JA, Nathan CF, Lima CD. Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis. J Biol Chem. 2005 Oct 7;280(40):33977-83. Epub 2005 Aug 10. PMID:16093239 doi:10.1074/jbc.M507466200