ATP-Driven Electron Transfer in the DCCP:DCCP-R Protein: A Synergy of Conformational Shift and Asp–Arg Bridge Protonation for Redox Modulation
Year: 2026
Type: preprint
Abstract: Most enzymatic systems that couple ATP hydrolysis to low-potential electron transfer (ET) typically rely on: (i) large conformational changes that tune the redox properties of the reductase Fe-S cluster, and (ii) redox state-dependent dissociation of the reductase subunit to ensure directionality. The double-cubane cluster protein (DCCP) and its reductase (DCCP-R) operate through a distinct mechanism, as the complex remains associated and the crystal structures reveal only subtle nucleotide-dependent conformational changes. These include the formation of Asp–Arg salt bridges by two aspartates (Asp113), located next to the [4Fe4S] cluster at the DCCP:DCCP-R interface. Infrared spectroscopy further showed that protein scaffold rearrangements are rate-limiting and likely involve carboxylate protonation dynamics. In addition, direct electrochemistry revealed an unusually high midpoint potential for a low-potential [4Fe4S] cluster. DFT modeling demonstrated that the ATP-dependent conformational change is coupled to the protonation status of Asp113 in proximity to the [4Fe4S] electron relay. This coupling modulates the cluster redox behavior in an electrostatic proton-coupled ET (PCET) manner, providing a thermodynamic basis for electron transfer to the low-potential [8Fe9S] cluster in DCCP.
Source: ChemRxiv
Language: English
Field: Energy
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7214600015