+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Structure, biochemistry, and inhibition of essential 4'-phosphopantetheinyl transferases from two species of Mycobacteria



Structure, biochemistry, and inhibition of essential 4'-phosphopantetheinyl transferases from two species of Mycobacteria



Acs Chemical Biology 9(9): 1939-1944



4'-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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 055960085

Download citation: RISBibTeXText

PMID: 24963544

DOI: 10.1021/cb500263p


Related references

The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proceedings of the National Academy of Sciences of the United States of America 103(22): 8511-8516, 2006

Structure-based mutational analysis of the 4'-phosphopantetheinyl transferases Sfp from Bacillus subtilis: carrier protein recognition and reaction mechanism. Biochemistry 43(14): 4128-4136, 2004

Phosphopantetheinyl transferases and uses thereof. Official Gazette of the United States Patent & Trademark Office Patents 1271(3), 2003

A new enzyme superfamily: The phosphopantetheinyl transferases. Chemistry and Biology 3(11): 923-936, 1996

Use of motif scanning to identify Phosphopantetheinyl transferases in yeast and man. American Journal of Human Genetics 73(5): 421, 2003

Two Functionally Distinctive Phosphopantetheinyl Transferases from Amoeba Dictyostelium discoideum. PLoS ONE 6(9): e24262, 1-10, 2011

Characterization and evolutionary implications of the triad Asp-Xxx-Glu in group II phosphopantetheinyl transferases. Plos one 9(7): E103031, 2014

Two functionally distinctive phosphopantetheinyl transferases from amoeba Dictyostelium discoideum. Plos one 6(9): E24262, 2011

The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life. Natural Product Reports 31(1): 61, 2014

Improvement of natamycin production by engineering of phosphopantetheinyl transferases in Streptomyces chattanoogensis L10. Applied and Environmental Microbiology 79(11): 3346-3354, 2013

Efficient Preparation of Site-Specific Antibody-Drug Conjugates Using Phosphopantetheinyl Transferases. Bioconjugate Chemistry 26(12): 2554-2562, 2015

Characterization of the phosphopantetheinyl transferases Sfp and LpaB3 from surfactin- and iturin-producing strains of Bacillus subtilis. Abstracts of the General Meeting of the American Society for Microbiology 97: 351, 1997

Two functionally redundant Sfp-type 4'-phosphopantetheinyl transferases differentially activate biosynthetic pathways in Myxococcus xanthus. Chembiochem 9(10): 1549-1553, 2008