Flavin Binding to the Deca-heme Cytochrome MtrC: Insights from Computational Molecular Simulation

Area of Science:

• Microbial electrochemistry
• Biochemistry
• Structural biology

Background:

• Dissimilatory bacteria respire using extracellular metal oxides instead of oxygen.
• Outer-membrane multiheme cytochromes and secreted flavins facilitate this extracellular respiration.
• The molecular-level interaction between cytochromes and flavins remains unclear.

Purpose of the Study:

• To investigate the interaction between the deca-heme cytochrome MtrC and flavin mononucleotide (FMN).
• To determine the binding affinity and site of MtrC-FMN interaction using computational methods.
• To understand the role of this interaction in extracellular respiration.

Main Methods:

• Computational docking of MtrC and FMN.
• Analysis of binding site and hydrogen bonding.
• Molecular dynamics simulations to explore conformational changes.

Main Results:

• FMN binds MtrC weakly, with a dissociation constant (Kd) of 490 μM, near heme 2.
• Binding is weaker than typical FMN-binding proteins due to fewer hydrogen bonds.
• Molecular dynamics suggest potential conformational changes but no increased binding affinity upon disulfide bond cleavage.

Conclusions:

• MtrC-FMN binding is reversible and not highly specific.
• This weak, non-specific binding supports FMN's function as a redox shuttle in extracellular respiration.
• Further research into cytochrome-flavin interactions is needed to fully elucidate extracellular electron transfer mechanisms.