The X-ray crystal structure of BorF, the flavin reductase subunit of a two-component flavin-dependent tryptophan halogenase.

BorF is a short-chain flavin reductase from a desert soil bacterium that uses NADH to reduce FAD to FADH, which is used by the tryptophan-6-halogenase BorH to chlorinate tryptophan in the biosynthetic pathway of borregomycin A. The X-ray crystal structure of BorF bound to FAD was solved to 2.37 Å by molecular replacement and consists of a homodimer of single-domain protomers with a Greek key split β-barrel topology containing a domain-swapped N-terminal α-helix, as seen in other members of this family. Insertions and deletions in the region between α3 and β5 lead to a variety of different conformations of the adenosine portion of FAD bound to BorF and structurally related reductases. Comparison of the FAD-bound structures of BorF and BorH suggests that FAD must completely dissociate from BorH in order to be reduced by BorF.