Why WrbA is weaker than flavodoxin in binding FMN. A molecular modeling study

The protein WrbA from Escherichia coli is the founding member of a class of novel multimeric flavodoxin-like proteins implicated in defense against oxidative stress. Although, WrbA is predicted to share the twisted α/β open-sheet fold of the flavodoxins and to bind flavin mononucleotide (FMN) as its physiological cofactor, the binding is much weaker in comparison with flavodoxin (the binding constants are ∼2 μM for WrbA and ∼1 nM for flavodoxin). To elucidate the different FMN-binding behaviors of WrbA and flavodoxin, we modeled the WrbA structure and examined its interactions with FMN by docking experiments, and then compared them with those at the flavodoxin active site. The results provide a rationale for the reduced cofactor affinity displayed by WrbA relative to flavodoxin.