8APR

CaMct - Mesaconyl-CoA C1:C4 CoA Transferase of Chloroflexus aurantiacus

8APR の概要

• エントリーDOI: 10.2210/pdb8apr/pdb
• 分子名称: 2-methylfumaryl-CoA isomerase, CHLORIDE ION (3 entities in total)
• 機能のキーワード: mesaconyl-coa, methylfumaryl-coa, isomerase, intramolecular, methylfumaryl-coa isomerase, 3-hydroxypropionate, 3ohp, transferase
• 由来する生物種: Chloroflexus aurantiacus J-10-fl
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 142312.94

構造登録者

Pfister, P.,Zarzycki, J.,Erb, T.J. (登録日: 2022-08-10, 公開日: 2022-12-28, 最終更新日: 2024-01-31)

主引用文献

Pfister, P.,Zarzycki, J.,Erb, T.J.
Structural Basis for a Cork-Up Mechanism of the Intra-Molecular Mesaconyl-CoA Transferase.
Biochemistry, 62:75-84, 2023

PubMed Abstract: Mesaconyl-CoA transferase (Mct) is one of the key enzymes of the 3-hydroxypropionate (3HP) bi-cycle for autotrophic CO 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 M s. 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 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.

PubMed: 36535006
DOI: 10.1021/acs.biochem.2c00532

実験手法

X-RAY DIFFRACTION (2.1 Å)