8apr

Publication Abstract from PubMed

Mesaconyl-CoA transferase (Mct) is one of the key enzymes of the 3-hydroxypropionate (3HP) bi-cycle for autotrophic CO(2) fixation. Mct is a family III/Frc family CoA transferase that catalyzes an unprecedented intra-molecular CoA transfer from the C1-carboxyl group to the C4-carboxyl group of mesaconate at catalytic efficiencies >10(6) M(-1) s(-1). Here, we show that the reaction of Mct proceeds without any significant release of free CoA or the transfer to external acceptor acids. Mct catalyzes intra-molecular CoA transfers at catalytic efficiencies that are at least more than 6 orders of magnitude higher compared to inter-molecular CoA transfers, demonstrating that the enzyme exhibits exquisite control over its reaction. To understand the molecular basis of the intra-molecular CoA transfer in Mct, we solved crystal structures of the enzyme from Chloroflexus aurantiacus in its apo form, as well as in complex with mesaconyl-CoA and several covalently enzyme-bound intermediates of CoA and mesaconate at the catalytically active residue Asp165. Based on these structures, we propose a reaction mechanism for Mct that is similar to inter-molecular family III/Frc family CoA transferases. However, in contrast to the latter that undergo opening and closing cycles during the reaction to exchange substrates, the central cavity of Mct remains sealed ("corked-up") by the CoA moiety, strongly favoring the intra-molecular CoA transfer between the C1 and the C4 position of mesaconate.

Structural Basis for a Cork-Up Mechanism of the Intra-Molecular Mesaconyl-CoA Transferase.,Pfister P, Zarzycki J, Erb TJ Biochemistry. 2022 Dec 19. doi: 10.1021/acs.biochem.2c00532. PMID:36535006^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.