|4kq2, resolution 2.95Å ()|
|Ligands:||, , , ,|
|Related:|| 4kq1, 4kqm
Glucose1,2cyclic phosphate bound activated state of Yeast Glycogen Synthase
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-A resolution structure of the complex with UMP/GCP and a 2.8-A 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 UDPglucose complex was found to be 13.3 degrees more closed compared with a UDP complex. However, the UMPGCP complex was 4.8 degrees less closed than the glucose complex, which may explain the low efficiency of GCP transfer. Modeling of either alpha- or beta-glucose or a mixture of both anomers can account for the observed electron density of the UDPglucose 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.
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. 2013 Dec 24;110(52):20976-81. doi:, 10.1073/pnas.1310106111. Epub 2013 Dec 9. PMID:24324135
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
4kq2 is a 4 chain structure. Full crystallographic information is available from OCA.
- Chikwana VM, Khanna M, Baskaran S, Tagliabracci VS, Contreras CJ, Depaoli-Roach A, Roach PJ, Hurley TD. Structural basis for 2'-phosphate incorporation into glycogen by glycogen synthase. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):20976-81. doi:, 10.1073/pnas.1310106111. Epub 2013 Dec 9. PMID:24324135 doi:http://dx.doi.org/10.1073/pnas.1310106111