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Publication Abstract from PubMed

Treponema pallidum (Tp), an obligate parasite of humans and the causative agent of syphilis, has evolved the capacity to exploit host-derived metabolites for its survival. Flavin-containing compounds are essential cofactors that are required for metabolic processes in all living organisms, and riboflavin is a direct precursor of the cofactors FMN and FAD. Unlike many pathogenic bacteria, Tp cannot synthesize riboflavin; we recently described a flavin-uptake mechanism comprised of an ABC-type transporter. However, there is a paucity of information about flavin utilization in bacterial periplasms. Using a discovery-driven approach, we have identified the TP0796 lipoprotein as a previously uncharacterized Mg2+-dependent FAD pyrophosphatase within the ApbE superfamily. TP0796 likely plays a central role in flavin turnover by hydrolyzing exogenously acquired FAD yielding AMP and FMN. Biochemical and structural investigations revealed that the enzyme has a unique bimetal Mg2+catalytic center. Furthermore, the pyrophosphatase activity is product inhibited by AMP, indicating a possible role for this molecule in modulating FMN and FAD levels in the treponemal periplasm. The ApbE superfamily was previously thought to be involved in thiamine biosynthesis, but our characterization of TP0796 prompts a re-naming of this superfamily as a periplasmic FAD processing protein (Fpp). TP0796 is the first structurally and biochemically characterized FAD pyrophosphate enzyme in bacteria. This new paradigm for a bacterial flavin-utilization pathway may prove to be useful for future inhibitor design.

The TP0796 lipoprotein of Treponema pallidum is a bimetal-dependent FAD pyrophosphatase with a potential role in flavin homeostasis.,Deka RK, Brautigam CA, Liu WZ, Tomchick DR, Norgard MV J Biol Chem. 2013 Feb 27. PMID:23447540^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.