9KRV

B. bacteriovorus MaeB acetyl-CoA bound form

9KRV の概要

• エントリーDOI: 10.2210/pdb9krv/pdb
• EMDBエントリー: 62542
• 分子名称: NADP-dependent malic enzyme, ACETYL COENZYME *A, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, cryo-em, allostery, structural protein
• 由来する生物種: Bdellovibrio bacteriovorus
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 517397.24

構造登録者

Sassa, M.,Yamato, H.,Tanino, H.,Fukuda, Y.,Inoue, T. (登録日: 2024-11-28, 公開日: 2025-12-03, 最終更新日: 2025-12-10)

主引用文献

Sassa, M.,Yamato, H.,Tanino, H.,Fukuda, Y.,Inoue, T.
Divergent acetyl-CoA binding modes mediate allosteric inhibition of bacterial hybrid-type malic enzymes.
J.Biol.Chem., 301:110887-110887, 2025

PubMed Abstract: Malic enzymes (MEs) function as the bypass enzyme in the Krebs cycle and have attracted attention in a wide range of scientific and industrial fields. In contrast to eukaryotic MEs, there is currently a lack of understanding of the structure-function relationships of prokaryotic MEs. Especially, little is known about an allosteric inhibition mechanism by an effector ligand in multi-domain MEs called hybrid-type MEs. Many bacterial hybrid-type MEs are inhibited by acetyl-CoA; however, the proposed acetyl-CoA binding site is not conserved. Here, we determined crystal and cryo-EM structures of hybrid-type MEs from Escherichia coli (EcMaeB) and Bdellovibrio bacteriovorus including complexes with acetyl-CoA. They reveal that these MaeBs have totally different acetyl-CoA binding sites and show different overall structural changes. However, the binding acetyl-CoA molecules induce identical movements of several α helices near the ligand both in EcMaeB and BbMaeB. Enzymatic assays proved that residues at the acetyl-CoA binding site are needed for inhibition. Phylogenetic analysis uncovered that EcMaeB and BbMaeB are classified into different clades of hybrid-type MEs and that the amino acid residues at the acetyl-CoA binding sites in different clades have evolved exclusively from each other. These results not only provide insights into bacterial MEs but also expand our knowledge about allosteric regulation in enzymes.

PubMed: 41197718
DOI: 10.1016/j.jbc.2025.110887

実験手法

ELECTRON MICROSCOPY (3.18 Å)