Molecular insights into the binding of coenzyme F420 to the conserved protein Rv1155 from Mycobacterium tuberculosis

Coenzyme F-420 is a deazaflavin hydride carrier with a lower reduction potential than most flavins. In Mycobacterium tuberculosis (Mtb), F-420 plays an important role in activating PA-824, an antituberculosis drug currently used in clinical trials. Although F-420 is important to Mtb redox metabolism, little is known about the enzymes that bind F-420 and the reactions that they catalyze. We have identified a novel F-420-binding protein, Rv1155, which is annotated in the Mtb genome sequence as a putative flavin mononucleotide (FMN)-binding protein. Using biophysical techniques, we have demonstrated that instead of binding FMN or other flavins, Rv1155 binds coenzyme F-420. The crystal structure of the complex of Rv1155 and F-420 reveals one F-420 molecule bound to each monomer of the Rv1155 dimer. Structural, biophysical, and bioinformatic analyses of the Rv1155-F-420 complex provide clues about its role in the bacterium.