4C4R

Structure of beta-phosphoglucomutase in complex with a phosphonate analogue of beta-glucose-1-phosphate and magnesium trifluoride

Summary for 4C4R

• Entry DOI: 10.2210/pdb4c4r/pdb
• Related: 4C4S 4C4T
• Descriptor: BETA-PHOSPHOGLUCOMUTASE, MAGNESIUM ION, (1R)-1,5-anhydro-1-(phosphonomethyl)-D-glucitol, ... (5 entities in total)
• Functional Keywords: phosphoryl transfer, transition state, metal fluoride, mutase, isomerase
• Biological source: LACTOCOCCUS LACTIS
• Cellular location: Cytoplasm (Potential): P71447
• Total number of polymer chains: 1
• Total formula weight: 24603.36

Authors

Pellegrini, E.,Bowler, M.W. (deposition date: 2013-09-09, release date: 2014-07-16, Last modification date: 2023-12-20)

Primary citation

Jin, Y.,Bhattasali, D.,Pellegrini, E.,Forget, S.M.,Baxter, N.J.,Cliff, M.J.,Bowler, M.W.,Jakeman, D.L.,Blackburn, G.M.,Waltho, J.P.
Alpha-Fluorophosphonates Reveal How a Phosphomutase Conserves Transition State Conformation Over Hexose Recognition in its Two-Step Reaction.
Proc.Natl.Acad.Sci.USA, 111:12384-, 2014

PubMed Abstract: β-Phosphoglucomutase (βPGM) catalyzes isomerization of β-D-glucose 1-phosphate (βG1P) into D-glucose 6-phosphate (G6P) via sequential phosphoryl transfer steps using a β-D-glucose 1,6-bisphosphate (βG16BP) intermediate. Synthetic fluoromethylenephosphonate and methylenephosphonate analogs of βG1P deliver novel step 1 transition state analog (TSA) complexes for βPGM, incorporating trifluoromagnesate and tetrafluoroaluminate surrogates of the phosphoryl group. Within an invariant protein conformation, the β-D-glucopyranose ring in the βG1P TSA complexes (step 1) is flipped over and shifted relative to the G6P TSA complexes (step 2). Its equatorial hydroxyl groups are hydrogen-bonded directly to the enzyme rather than indirectly via water molecules as in step 2. The (C)O-P bond orientation for binding the phosphate in the inert phosphate site differs by ∼ 30° between steps 1 and 2. By contrast, the orientations for the axial O-Mg-O alignment for the TSA of the phosphoryl group in the catalytic site differ by only ∼ 5°, and the atoms representing the five phosphorus-bonded oxygens in the two transition states (TSs) are virtually superimposable. The conformation of βG16BP in step 1 does not fit into the same invariant active site for step 2 by simple positional interchange of the phosphates: the TS alignment is achieved by conformational change of the hexose rather than the protein.

PubMed: 25104750
DOI: 10.1073/PNAS.1402850111

Experimental method

X-RAY DIFFRACTION (1.1 Å)