8QMF

Transketolase from Vibrio vulnificus in complex with thiamin pyrophosphate

Summary for 8QMF

• Entry DOI: 10.2210/pdb8qmf/pdb
• Descriptor: Transketolase 2, THIAMINE DIPHOSPHATE, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: transketolase, infectious bacteria, pentose phosphate pathway, vibrio vulnificus, cytosolic protein
• Biological source: Vibrio vulnificus YJ016
• Total number of polymer chains: 2
• Total formula weight: 149650.87

Authors

Ballut, L.,Georges, R.N.,Octobre, G.,Charmantray, F.,Doumeche, B. (deposition date: 2023-09-22, release date: 2024-02-07, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)