The crystal structure of the conserved hypothetical protein Rv2991 from Mycobacterium tuberculosis has been solved by SAD using seleno-methionine substituted protein. The dimeric biological assembly and the sequence and fold conservation are typical of F-420 cofactor binding enzymes. Despite Rv2991 still being of unknown function, sequence and structural comparison with similar proteins enable a role to be proposed for its C terminal stretch of residues in recognizing and orienting the substrate. In addition, the C-terminus is involved in both protein folding and determining the size of the active site cavity.