6ydk | pdb_00006ydk
Substrate-free P146A variant of beta-phosphoglucomutase from Lactococcus lactis
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 PubMedEnzyme regulation is vital for metabolic adaptability in living systems. Fine control of enzyme activity is often delivered through post-translational mechanisms, such as allostery or allokairy. beta-phosphoglucomutase (betaPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for complete catabolism of trehalose and maltose, through the isomerisation of beta-glucose 1-phosphate to glucose 6-phosphate via beta-glucose 1,6-bisphosphate. Surprisingly for a gatekeeper of glycolysis, no fine control mechanism of betaPGM has yet been reported. Herein, we describe allomorphy, a post-translational control mechanism of enzyme activity. In betaPGM, isomerisation of the K145-P146 peptide bond results in the population of two conformers that have different activities owing to repositioning of the K145 sidechain. In vivo phosphorylating agents, such as fructose 1,6-bisphosphate, generate phosphorylated forms of both conformers, leading to a lag phase in activity until the more active phosphorylated conformer dominates. In contrast, the reaction intermediate beta-glucose 1,6-bisphosphate, whose concentration depends on the beta-glucose 1-phosphate concentration, couples the conformational switch and the phosphorylation step, resulting in the rapid generation of the more active phosphorylated conformer. In enabling different behaviours for different allomorphic activators, allomorphy allows an organism to maximise its responsiveness to environmental changes while minimising the diversion of valuable metabolites. Allomorphy as a mechanism of post-translational control of enzyme activity.,Wood HP, Cruz-Navarrete FA, Baxter NJ, Trevitt CR, Robertson AJ, Dix SR, Hounslow AM, Cliff MJ, Waltho JP Nat Commun. 2020 Nov 2;11(1):5538. doi: 10.1038/s41467-020-19215-9. PMID:33139716[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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