3QVB

Crystal Structure of Human Glycogenin-1 (GYG1) complexed with manganese and UDP

Summary for 3QVB

• Entry DOI: 10.2210/pdb3qvb/pdb
• Related: 3Q4S
• Descriptor: Glycogenin-1, MANGANESE (II) ION, URIDINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: structural genomics, structural genomics consortium, (sgc), transferase, glycosyltransferase, glycogen biosynthesis, glycosylation
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 30365.08

Authors

Chaikuad, A.,Froese, D.S.,Yue, W.W.,Krysztofinska, E.,von Delft, F.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Oppermann, U.,Structural Genomics Consortium (SGC) (deposition date: 2011-02-25, release date: 2011-03-23, Last modification date: 2023-09-13)

Primary citation

Chaikuad, A.,Froese, D.S.,Berridge, G.,von Delft, F.,Oppermann, U.,Yue, W.W.
Conformational plasticity of glycogenin and its maltosaccharide substrate during glycogen biogenesis.
Proc.Natl.Acad.Sci.USA, 108:21028-21033, 2011

PubMed Abstract: Glycogenin initiates the synthesis of a maltosaccharide chain covalently attached to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen synthesis. We have captured crystallographic snapshots of human glycogenin during its reaction cycle, revealing a dynamic conformational switch between ground and active states mediated by the sugar donor UDP-glucose. This switch includes the ordering of a polypeptide stretch containing Tyr195, and major movement of an approximately 30-residue "lid" segment covering the active site. The rearranged lid guides the nascent maltosaccharide chain into the active site in either an intra- or intersubunit mode dependent upon chain length and steric factors and positions the donor and acceptor sugar groups for catalysis. The Thr83Met mutation, which causes glycogen storage disease XV, is conformationally locked in the ground state and catalytically inactive. Our data highlight the conformational plasticity of glycogenin and coexistence of two modes of glucosylation as integral to its catalytic mechanism.

PubMed: 22160680
DOI: 10.1073/pnas.1113921108

Experimental method

X-RAY DIFFRACTION (2.26 Å)