Brucella melitensis is the etiological agent responsible for
brucellosis. Present in the B. melitensis genome is a 116-residue
protein related to
arsenate reductases (Bm-YffB; BR0369).
Arsenate reductases (ArsC) convert
arsenate ion (H(2)AsO(4)(-)), a compound that is toxic to bacteria, to
arsenite ion (AsO(2)(-)), a product that may be efficiently exported out of the cell. Consequently, Bm-YffB is a potential
drug target because if
arsenate reduction is the
protein's major
biological function then disabling the cell's ability to reduce
arsenate would make these cells more sensitive to the deleterious effects of
arsenate. Size-exclusion chromatography and NMR spectroscopy indicate that Bm-YffB is a monomer in
solution. The
solution structure of Bm-YffB (PDB entry 2kok) shows that the
protein consists of two domains: a four-stranded mixed β-sheet flanked by two α-helices on one side and an α-helical bundle. The α/β domain is characteristic of the fold of
thioredoxin-like
proteins and the overall structure is generally similar to those of known
arsenate reductases despite the marginal sequence similarity. Chemical shift perturbation studies with (15)N-labeled Bm-YffB show that the
protein binds
reduced glutathione at a site adjacent to a region similar to the HX(3)CX(3)R catalytic sequence motif that is important for
arsenic detoxification activity in the classical
arsenate-reductase family of
proteins. The latter observation supports the hypothesis that the ArsC-YffB family of
proteins may function as
glutathione-dependent
thiol reductases. However, comparison of the structure of Bm-YffB with the structures of
proteins from the classical ArsC family suggest that the mechanism and possibly the function of Bm-YffB and other related
proteins (ArsC-YffB) may differ from those of the ArsC family of
proteins.