4kq2 Citations

Structural basis for 2'-phosphate incorporation into glycogen by glycogen synthase.

Proc Natl Acad Sci U S A 110 20976-81 (2013)
Related entries: 4kq1, 4kqm

Cited: 15 times
EuropePMC logo PMID: 24324135

Abstract

Glycogen is a glucose polymer that contains minor amounts of covalently attached phosphate. Hyperphosphorylation is deleterious to glycogen structure and can lead to Lafora disease. Recently, it was demonstrated that glycogen synthase catalyzes glucose-phosphate transfer in addition to its characteristic glucose transfer reaction. Glucose-1,2-cyclic-phosphate (GCP) was proposed to be formed from UDP-Glc breakdown and subsequently transferred, thus providing a source of phosphate found in glycogen. To gain further insight into the molecular basis for glucose-phosphate transfer, two structures of yeast glycogen synthase were determined; a 3.0-Å resolution structure of the complex with UMP/GCP and a 2.8-Å resolution structure of the complex with UDP/glucose. Structural superposition of the complexes revealed that the bound ligands and most active site residues are positioned similarly, consistent with the use of a common transfer mechanism for both reactions. The N-terminal domain of the UDP-glucose complex was found to be 13.3° more closed compared with a UDP complex. However, the UMP · GCP complex was 4.8° less closed than the glucose complex, which may explain the low efficiency of GCP transfer. Modeling of either α- or β-glucose or a mixture of both anomers can account for the observed electron density of the UDP-glucose complex. NMR studies of UDP-Glc hydrolysis by yeast glycogen synthase were used to verify the stereochemistry of the product, and they also showed synchronous GCP accumulation. The similarities in the active sites of glycogen synthase and glycogen phosphorylase support the idea of a common catalytic mechanism in GT-B enzymes independent of the specific reaction catalyzed.

Articles - 4kq2 mentioned but not cited (1)

  1. Structural basis for 2'-phosphate incorporation into glycogen by glycogen synthase. Chikwana VM, Khanna M, Baskaran S, Tagliabracci VS, Contreras CJ, DePaoli-Roach A, Roach PJ, Hurley TD. Proc Natl Acad Sci U S A 110 20976-20981 (2013)


Reviews citing this publication (4)

  1. Glycogen metabolism in humans. Adeva-Andany MM, González-Lucán M, Donapetry-García C, Fernández-Fernández C, Ameneiros-Rodríguez E. BBA Clin 5 85-100 (2016)
  2. Lafora disease offers a unique window into neuronal glycogen metabolism. Gentry MS, Guinovart JJ, Minassian BA, Roach PJ, Serratosa JM. J Biol Chem 293 7117-7125 (2018)
  3. Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function. Zhao H, Raines LN, Huang SC. Cells 9 E562 (2020)
  4. Structural biology of glucan phosphatases from humans to plants. Gentry MS, Brewer MK, Vander Kooi CW. Curr Opin Struct Biol 40 62-69 (2016)

Articles citing this publication (10)

  1. Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase. Tang B, Frasinyuk MS, Chikwana VM, Mahalingan KK, Morgan CA, Segvich DM, Bondarenko SP, Mrug GP, Wyrebek P, Watt DS, DePaoli-Roach AA, Roach PJ, Hurley TD. J Med Chem 63 3538-3551 (2020)
  2. Glycogen phosphomonoester distribution in mouse models of the progressive myoclonic epilepsy, Lafora disease. DePaoli-Roach AA, Contreras CJ, Segvich DM, Heiss C, Ishihara M, Azadi P, Roach PJ. J Biol Chem 290 841-850 (2015)
  3. Brain glycogen serves as a critical glucosamine cache required for protein glycosylation. Sun RC, Young LEA, Bruntz RC, Markussen KH, Zhou Z, Conroy LR, Hawkinson TR, Clarke HA, Stanback AE, Macedo JKA, Emanuelle S, Brewer MK, Rondon AL, Mestas A, Sanders WC, Mahalingan KK, Tang B, Chikwana VM, Segvich DM, Contreras CJ, Allenger EJ, Brainson CF, Johnson LA, Taylor RE, Armstrong DD, Shaffer R, Waechter CJ, Vander Kooi CW, DePaoli-Roach AA, Roach PJ, Hurley TD, Drake RR, Gentry MS. Cell Metab 33 1404-1417.e9 (2021)
  4. Incorporation of phosphate into glycogen by glycogen synthase. Contreras CJ, Segvich DM, Mahalingan K, Chikwana VM, Kirley TL, Hurley TD, DePaoli-Roach AA, Roach PJ. Arch Biochem Biophys 597 21-29 (2016)
  5. Redox Switch for the Inhibited State of Yeast Glycogen Synthase Mimics Regulation by Phosphorylation. Mahalingan KK, Baskaran S, DePaoli-Roach AA, Roach PJ, Hurley TD. Biochemistry 56 179-188 (2017)
  6. Mechanism of glycogen synthase inactivation and interaction with glycogenin. Marr L, Biswas D, Daly LA, Browning C, Vial SCM, Maskell DP, Hudson C, Bertrand JA, Pollard J, Ranson NA, Khatter H, Eyers CE, Sakamoto K, Zeqiraj E. Nat Commun 13 3372 (2022)
  7. Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate. McCorvie TJ, Loria PM, Tu M, Han S, Shrestha L, Froese DS, Ferreira IM, Berg AP, Yue WW. Nat Struct Mol Biol 29 628-638 (2022)
  8. Synthesis of a non-natural glucose-2-phosphate ester able to dupe the acc system of Agrobacterium fabrum. Li SZ, Vigouroux A, Ahmar M, El Sahili A, Soulère L, Sago L, Cornu D, Moréra S, Queneau Y. Org Biomol Chem 17 1090-1096 (2019)
  9. Crystal structures of glycogen-debranching enzyme mutants in complex with oligosaccharides. Shen M, Gong X, Xiang S. Acta Crystallogr F Struct Biol Commun 77 420-426 (2021)
  10. Esters of Glucose-2-Phosphate: Occurrence and Chemistry. Zhang Q, Li SZ, Ahmar M, Soulère L, Queneau Y. Molecules 25 E2829 (2020)