4qjk
From Proteopedia
Crystal structure of M. tuberculosis phosphopantetheinyl transferase PptT
Structural highlights
FunctionPPTT_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] Publication Abstract from PubMed4'-Phosphopantetheinyl transferases (PPTase) post-translationally modify carrier proteins with a phosphopantetheine moiety, an essential reaction in all three domains of life. In the bacterial genus Mycobacteria, the Sfp-type PPTase activates pathways necessary for the biosynthesis of cell wall components and small molecule virulence factors. We solved the X-ray crystal structures and biochemically characterized the Sfp-type PPTases from two of the most prevalent Mycobacterial pathogens, PptT of M. tuberculosis and MuPPT of M. ulcerans. Structural analyses reveal significant differences in cofactor binding and active site composition when compared to previously characterized Sfp-type PPTases. Functional analyses including the efficacy of Sfp-type PPTase-specific inhibitors also suggest that the Mycobacterial Sfp-type PPTases can serve as therapeutic targets against Mycobacterial infections. Structure, Biochemistry, and Inhibition of Essential 4'-Phosphopantetheinyl Transferases from Two Species of Mycobacteria.,Vickery CR, Kosa NM, Casavant EP, Duan S, Noel JP, Burkart MD ACS Chem Biol. 2014 Jul 9. PMID:24963544[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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