6WF7

Methylmalonyl-CoA epimerase in complex with methylmalonyl-CoA and NH4+

6WF7 の概要

• エントリーDOI: 10.2210/pdb6wf7/pdb
• 分子名称: Methylmalonyl-CoA epimerase, AMMONIUM ION, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: epimerase, acid-base, enol, enolate, isomerase
• 由来する生物種: Streptomyces coelicolor
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18005.15

構造登録者

Stunkard, L.M.,Benjamin, A.B.,Bower, J.B.,Huth, T.J.,Lohman, J.R. (登録日: 2020-04-03, 公開日: 2020-07-08, 最終更新日: 2023-10-18)

主引用文献

Stunkard, L.M.,Benjamin, A.B.,Bower, J.B.,Huth, T.J.,Lohman, J.R.
Substrate Enolate Intermediate and Mimic Captured in the Active Site of Streptomyces coelicolor Methylmalonyl-CoA Epimerase.
Chembiochem, 23:e202100487-e202100487, 2022

PubMed Abstract: Methylmalonyl-CoA epimerase (MMCE) is proposed to use general acid-base catalysis, but the proposed catalytic glutamic acids are highly asymmetrical in the active site unlike many other racemases. To gain insight into the puzzling relationships between catalytic mechanism, structure, and substrate preference, we solved Streptomyces coelicolor MMCE structures with substrate or 2-nitropropionyl-CoA, an intermediate/transition state analogue. Both ligand bound structures have a planar methylmalonate/2-nitropropionyl moiety indicating a deprotonated C2 with ≥4 Å distances to either catalytic acid. Both glutamates interact with the carboxylate/nitro group, either directly or through other residues. This suggests the proposed catalytic acids sequentially catalyze proton shifts between C2 and carboxylate of the substrate with an enolate intermediate. In addition, our structures provide a platform to design mutations for expanding substrate scope to support combinatorial biosynthesis.

PubMed: 34856049
DOI: 10.1002/cbic.202100487

実験手法

X-RAY DIFFRACTION (1.55 Å)