8QMF

Transketolase from Vibrio vulnificus in complex with thiamin pyrophosphate

8QMF の概要

• エントリーDOI: 10.2210/pdb8qmf/pdb
• 分子名称: Transketolase 2, THIAMINE DIPHOSPHATE, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: transketolase, infectious bacteria, pentose phosphate pathway, vibrio vulnificus, cytosolic protein
• 由来する生物種: Vibrio vulnificus YJ016
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 149650.87

構造登録者

Ballut, L.,Georges, R.N.,Octobre, G.,Charmantray, F.,Doumeche, B. (登録日: 2023-09-22, 公開日: 2024-02-07, 最終更新日: 2024-02-28)

主引用文献

Georges, R.N.,Ballut, L.,Octobre, G.,Comte, A.,Hecquet, L.,Charmantray, F.,Doumeche, B.
Structural determination and kinetic analysis of the transketolase from Vibrio vulnificus reveal unexpected cooperative behavior.
Protein Sci., 33:e4884-e4884, 2024

PubMed Abstract: Vibrio vulnificus (vv) is a multidrug-resistant human bacterial pathogen whose prevalence is expected to increase over the years. Transketolases (TK), transferases catalyzing two reactions of the nonoxidative branch of the pentose-phosphate pathway and therefore linked to several crucial metabolic pathways, are potential targets for new drugs against this pathogen. Here, the vvTK is crystallized and its structure is solved at 2.1 Å. A crown of 6 histidyl residues is observed in the active site and expected to participate in the thiamine pyrophosphate (cofactor) activation. Docking of fructose-6-phosphate and ferricyanide used in the activity assay, suggests that both substrates can bind vvTK simultaneously. This is confirmed by steady-state kinetics showing a sequential mechanism, on the contrary to the natural transferase reaction which follows a substituted mechanism. Inhibition by the I38-49 inhibitor (2-(4-ethoxyphenyl)-1-(pyrimidin-2-yl)-1H-pyrrolo[2,3-b]pyridine) reveals for the first time a cooperative behavior of a TK and docking experiments suggest a previously undescribed binding site at the interface between the pyrophosphate and pyridinium domains.

PubMed: 38145310
DOI: 10.1002/pro.4884

実験手法

X-RAY DIFFRACTION (2.1 Å)