Structural insight into the high reduction potentials observed for Fusobacterium nucleatum flavodoxin.

ABSTRACT: Flavodoxins are small flavin mononucleotide (FMN)-containing proteins that mediate a variety of electron transfer processes. The primary sequence of flavodoxin from Fusobacterium nucleatum, a pathogenic oral bacterium, is marked with a number of distinct features including a glycine to lysine (K13) substitution in the highly conserved phosphate-binding loop (T/S-X-T-G-X-T), variation in the aromatic residues that sandwich the FMN cofactor, and a more even distribution of acidic and basic residues. The Eox/sq (oxidized/semiquinone; -43?mV) and Esq/hq (semiquinone/hydroquinone; -256?mV) are the highest recorded reduction potentials of known long-chain flavodoxins. These more electropositive values are a consequence of the apoprotein binding to the FMN hydroquinone anion with ~70-fold greater affinity compared to the oxidized form of the cofactor. Inspection of the FnFld crystal structure revealed the absence of a hydrogen bond between the protein and the oxidized FMN N5 atom, which likely accounts for the more electropositive Eox/sq . The more electropositive Esq/hq is likely attributed to only one negatively charged group positioned within 12?Å of the FMN N1. We show that natural substitutions of highly conserved residues partially account for these more electropositive reduction potentials.

SUBMITTER: Mothersole RG 

PROVIDER: S-EPMC6635775 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature