8Q1C

Substrate-free D10N,P146A variant of beta-phosphoglucomutase from Lactococcus lactis

Summary for 8Q1C

• Entry DOI: 10.2210/pdb8q1c/pdb
• Related: 2WHE 6H93 6YDK
• Descriptor: Beta-phosphoglucomutase, MAGNESIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: mutase, isomerase
• Biological source: Lactococcus lactis subsp. lactis Il1403
• Total number of polymer chains: 2
• Total formula weight: 48970.05

Authors

Cruz-Navarrete, F.A.,Baxter, N.J.,Flinders, A.J.,Buzoianu, A.,Cliff, M.J.,Baker, P.J.,Waltho, J.P. (deposition date: 2023-07-31, release date: 2024-08-07)

Primary citation

Cruz-Navarrete, F.A.,Baxter, N.J.,Flinders, A.J.,Buzoianu, A.,Cliff, M.J.,Baker, P.J.,Waltho, J.P.
Peri active site catalysis of proline isomerisation is the molecular basis of allomorphy in beta-phosphoglucomutase.
Commun Biol, 7:909-909, 2024

PubMed Abstract: Metabolic regulation occurs through precise control of enzyme activity. Allomorphy is a post-translational fine control mechanism where the catalytic rate is governed by a conformational switch that shifts the enzyme population between forms with different activities. β-Phosphoglucomutase (βPGM) uses allomorphy in the catalysis of isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate. Herein, we describe structural and biophysical approaches to reveal its allomorphic regulatory mechanism. Binding of the full allomorphic activator β-glucose 1,6-bisphosphate stimulates enzyme closure, progressing through NAC I and NAC III conformers. Prior to phosphoryl transfer, loops positioned on the cap and core domains are brought into close proximity, modulating the environment of a key proline residue. Hence accelerated isomerisation, likely via a twisted anti/C4-endo transition state, leads to the rapid predominance of active cis-P βPGM. In contrast, binding of the partial allomorphic activator fructose 1,6-bisphosphate arrests βPGM at a NAC I conformation and phosphoryl transfer to both cis-P βPGM and trans-P βPGM occurs slowly. Thus, allomorphy allows a rapid response to changes in food supply while not otherwise impacting substantially on levels of important metabolites.

PubMed: 39068257
DOI: 10.1038/s42003-024-06577-9

Experimental method

X-RAY DIFFRACTION (1.679 Å)