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Molecular insights into the binding of coenzyme F 420 to the conserved protein R v1155 from M ycobacterium tuberculosis
Author(s) -
Mashalidis Ellene H.,
Gittis Apostolos G.,
Tomczak Aurelie,
Abell Chris,
Barry Clifton E.,
Garboczi David N.
Publication year - 2015
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2645
Subject(s) - flavin mononucleotide , flavin group , cofactor , mycobacterium tuberculosis , chemistry , biochemistry , coenzyme a , dimer , binding site , enzyme , stereochemistry , biology , tuberculosis , medicine , pathology , reductase , organic chemistry
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.