Nature Communications 5 (2014) 4626.

ATP-induced electron transfer by redox-selective partner recognition

Sandra E. Hennig^a, Sebastian Goetzl^a, Jae-Hun Jeoung^a, Martin Bommer^a, Friedhelm Lendzian^b, Peter Hildebrandt^b, Holger Dobbek^a*

^a Humboldt Universität zu Berlin, Institut für Biologie, Strukturbiologie/Biochemie, Unter den Linden 6, 10099 Berlin, Germany
^b Technische Universität Berlin, Institut für Chemie, Sekr. PC14, Strasse des 17. Juni 135, 10623 Berlin, Germany

* Corresponding author: Holger Dobbek, Humboldt Universität zu Berlin, Institut für Biologie, Strukturbiologie/Biochemie, Unter den Linden 6, 10099 Berlin, Germany

E-mail: holger.dobbek@biologie.hu-berlin.de
Phone: +49(0)30-2093-6369

Abstract

Enzymes provide a scaffold of chemical groups in precise arrangements, which allow them to lower the activation energy of chemical reactions. Such molecular machines are able to carry out highly energy-demanding chemical processes at atmospheric (or physiological) conditions. More frequently than desired an enzyme is inactivated by an unwanted side reaction. In living organisms, where the synthesis of the enzyme and cofactor also presents a sizable up-front investment, repair systems exist for crucial enzymes.

A globally important process is the assimilation of atmospheric CO₂ into organic matter. Under anaerobic conditions, CO₂ may be assimilated to acetate through the microbial Wood-Ljungdahl pathway. "The corrinoid (B₁₂) and [4Fe-4S] cluster containing protein (CoFeSP) acts in the late steps of the pathway. CoFeSP accepts a methyl group from a methyl-tetrahydrofolate bound methyltransferase and transfers it to acetyl-CoA synthase, for which its B₁₂ cycles between the CH₃-Co³⁺ and Co¹⁺ active states. The energy-rich Co¹⁺ state of CoFeSP is prone to oxidation generating the [inactive] Co²⁺ state." Hennig & Jeoung et al. have previously identified an ATP-dependent rescue factor RACo (reductive activator of CoFeSP), which is able to return the B₁₂ cofactor to the active Co¹⁺ state (Structure of the Month November 2012, PNAS 2012). The authors now present the structure of the RACo-CoFeSP complex (Fig. 1) and propose a unique model for the ATP-dependent electron transfer to B₁₂, which is initially energetically uphill (Fig. 2). For this purpose, RACo manipulates the coordination state of the cofactor. Commonly, the active Co¹⁺ is tetra-coordinated (the B₁₂ corrin ring provides all four ligands), while inactive Co²⁺ is penta-coordinated with one external (e.g. water) ligand. RACo replaces the β-ligand with the side chain of its own serine 398, while encapsulating the B₁₂ and locking out water. In an ATP-energised conformational change the serine ligand is then forced from Co²⁺ in the absence of an alternative ligand, thus transiently creating an unstable tetra-coordinated Co²⁺, which is easily reduced to Co¹⁺ by an electron from RACos [2Fe-2S] cluster. (M.B. & S.H.)