7ABX

Perdeuterated E65Q-TIM complexed with 2-PHOSPHOGLYCOLIC ACID

7ABX の概要

• エントリーDOI: 10.2210/pdb7abx/pdb
• 分子名称: Triosephosphate isomerase, 2-PHOSPHOGLYCOLIC ACID (3 entities in total)
• 機能のキーワード: isomerase, glycolysis, tim, triosephosphate isomerase, transtition state, perdeuteration
• 由来する生物種: Leishmania mexicana
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27364.27

構造登録者

Kelpsas, V.,Caldararu, O.,von Wachenfeldt, C.,Oksanen, E. (登録日: 2020-09-09, 公開日: 2021-07-28, 最終更新日: 2024-05-01)

主引用文献

Kelpsas, V.,Caldararu, O.,Blakeley, M.P.,Coquelle, N.,Wierenga, R.K.,Ryde, U.,von Wachenfeldt, C.,Oksanen, E.
Neutron structures of Leishmania mexicana triosephosphate isomerase in complex with reaction-intermediate mimics shed light on the proton-shuttling steps.
Iucrj, 8:633-643, 2021

PubMed Abstract: Triosephosphate isomerase (TIM) is a key enzyme in glycolysis that catalyses the interconversion of glyceraldehyde 3-phosphate and dihydroxy-acetone phosphate. This simple reaction involves the shuttling of protons mediated by protolysable side chains. The catalytic power of TIM is thought to stem from its ability to facilitate the deprotonation of a carbon next to a carbonyl group to generate an enediolate intermediate. The enediolate intermediate is believed to be mimicked by the inhibitor 2-phosphoglycolate (PGA) and the subsequent enediol intermediate by phosphoglycolohydroxamate (PGH). Here, neutron structures of TIM have been determined with both inhibitors, and joint neutron/X-ray refinement followed by quantum refinement has been performed. The structures show that in the PGA complex the postulated general base Glu167 is protonated, while in the PGH complex it remains deprotonated. The deuteron is clearly localized on Glu167 in the PGA-TIM structure, suggesting an asymmetric hydrogen bond instead of a low-barrier hydrogen bond. The full picture of the active-site protonation states allowed an investigation of the reaction mechanism using density-functional theory calculations.

PubMed: 34258011
DOI: 10.1107/S2052252521004619

実験手法

X-RAY DIFFRACTION (1.2 Å)