4u89

Structural highlights

Function

PPTT_MYCTU Transfers the 4'-phosphopantetheine moiety from coenzyme A to a Ser of acyl-carrier-protein (PubMed:9831524, PubMed:16709676, PubMed:25785780, PubMed:28203522). Involved in post-translational modification of various type-I polyketide synthases required for the formation of both mycolic acids and lipid virulence factors (PubMed:16709676). Acts on Pks13, Mas, PpsA, PpsB, PpsC and PpsD (PubMed:16709676, PubMed:28203522). Also acts on AcpM, the meromycolate extension acyl carrier protein (PubMed:25785780). In addition, is involved in the activation of the acyl carrier protein MbtL and the nonribosomal peptides synthases MbtB and MbtE, which are involved in the biosynthesis of the siderophore mycobactin (PubMed:9831524, PubMed:28203522).^{[1] [2] [3] [4]} Required for the replication and survival of Mycobacterium during the acute and chronic phases of infection in mice.^[5]

References

1. ↑ Chalut C, Botella L, de Sousa-D'Auria C, Houssin C, Guilhot C. The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8511-6. doi:, 10.1073/pnas.0511129103. Epub 2006 May 18. PMID:16709676 doi:http://dx.doi.org/10.1073/pnas.0511129103
2. ↑ Zimhony O, Schwarz A, Raitses-Gurevich M, Peleg Y, Dym O, Albeck S, Burstein Y, Shakked Z. AcpM, the meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, is activated by the 4'-phosphopantetheinyl transferase PptT, a potential target of the multistep mycolic acid biosynthesis. Biochemistry. 2015 Apr 14;54(14):2360-71. doi: 10.1021/bi501444e. Epub 2015 Apr, 1. PMID:25785780 doi:http://dx.doi.org/10.1021/bi501444e
3. ↑ Jung J, Bashiri G, Johnston JM, Baker EN. Mass spectral determination of phosphopantetheinylation specificity for carrier proteins in Mycobacterium tuberculosis. FEBS Open Bio. 2016 Oct 24;6(12):1220-1226. doi: 10.1002/2211-5463.12140., eCollection 2016 Dec. PMID:28203522 doi:http://dx.doi.org/10.1002/2211-5463.12140
4. ↑ Quadri LE, Sello J, Keating TA, Weinreb PH, Walsh CT. Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem Biol. 1998 Nov;5(11):631-45. doi: 10.1016/s1074-5521(98)90291-5. PMID:9831524 doi:http://dx.doi.org/10.1016/s1074-5521(98)90291-5
5. ↑ Leblanc C, Prudhomme T, Tabouret G, Ray A, Burbaud S, Cabantous S, Mourey L, Guilhot C, Chalut C. 4'-Phosphopantetheinyl transferase PptT, a new drug target required for Mycobacterium tuberculosis growth and persistence in vivo. PLoS Pathog. 2012 Dec;8(12):e1003097. doi: 10.1371/journal.ppat.1003097. Epub, 2012 Dec 20. PMID:23308068 doi:http://dx.doi.org/10.1371/journal.ppat.1003097