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

Ma, Z.; Rady, E. W.; de Silva, A. J.; Bellizzi, J. J.

2025-08-12 biochemistry
10.1101/2025.08.09.669344 bioRxiv
Show abstract

BorF is a short-chain flavin reductase from a desert soil bacterium that uses NADH to reduce FAD to FADH2, 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 [A] by molecular replacement and consists of a homodimer of single-domain protomers with a Greek key split {beta}-barrel topology containing a domain-swapped N-terminal -helix, as seen in other members of this family. Insertions and deletions in the region between 3 and {beta}5 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.

Published in Proteins: Structure, Function, and Bioinformatics (predicted rank #6) · training set

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