4c4t
Structure of beta-phosphoglucomutase in complex with a phosphonate analogue of beta-glucose-1-phosphate and aluminium tetrafluorideStructure of beta-phosphoglucomutase in complex with a phosphonate analogue of beta-glucose-1-phosphate and aluminium tetrafluoride
Structural highlights
FunctionPGMB_LACLA Catalyzes the interconversion of D-glucose 1-phosphate (G1P) and D-glucose 6-phosphate (G6P), forming beta-D-glucose 1,6-(bis)phosphate (beta-G16P) as an intermediate. The beta-phosphoglucomutase (Beta-PGM) acts on the beta-C(1) anomer of G1P. Glucose or lactose are used in preference to maltose, which is only utilized after glucose or lactose has been exhausted. It plays a key role in the regulation of the flow of carbohydrate intermediates in glycolysis and the formation of the sugar nucleotide UDP-glucose.[1] [2] Publication Abstract from PubMedbeta-Phosphoglucomutase (betaPGM) catalyzes isomerization of beta-d-glucose 1-phosphate (betaG1P) into d-glucose 6-phosphate (G6P) via sequential phosphoryl transfer steps using a beta-d-glucose 1,6-bisphosphate (betaG16BP) intermediate. Synthetic fluoromethylenephosphonate and methylenephosphonate analogs of betaG1P deliver novel step 1 transition state analog (TSA) complexes for betaPGM, incorporating trifluoromagnesate and tetrafluoroaluminate surrogates of the phosphoryl group. Within an invariant protein conformation, the beta-d-glucopyranose ring in the betaG1P 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 approximately 30 degrees 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 approximately 5 degrees , and the atoms representing the five phosphorus-bonded oxygens in the two transition states (TSs) are virtually superimposable. The conformation of betaG16BP 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. alpha-Fluorophosphonates reveal how a phosphomutase conserves transition state conformation over hexose recognition in its two-step reaction.,Jin Y, Bhattasali D, Pellegrini E, Forget SM, Baxter NJ, Cliff MJ, Bowler MW, Jakeman DL, Blackburn GM, Waltho JP Proc Natl Acad Sci U S A. 2014 Aug 7. pii: 201402850. PMID:25104750[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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