PDBsum entry 4qlb

Transferase

PDB id: 4qlb

Contents

Protein chains

650 a.a.

34 a.a.

33 a.a.

35 a.a.

Ligands

SO4 ×10

GOL ×3

Waters ×113

PDB id:

4qlb

Name:

Transferase

Title:

Structural basis for the recruitment of glycogen synthase by glycogenin

Structure:

Probable glycogen [starch] synthase. Chain: a, c, d, b. Fragment: glycogen synthase. Engineered: yes. Mutation: yes. Protein gyg-1, isoform b. Chain: g, e, h, f. Fragment: glycogenin (residues 268-302). Engineered: yes.

Source:

Caenorhabditis elegans. Roundworm. Organism_taxid: 6239. Gene: gsy-1, y46g5a.31. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence of gyg-1 (amino acids 268-302) occurs naturally in c. Elegans

Resolution:

2.60Å R-factor: 0.180 R-free: 0.224

Authors:

E.Zeqiraj,A.Judd,F.Sicheri

Key ref:

E.Zeqiraj et al. (2014). Structural basis for the recruitment of glycogen synthase by glycogenin. Proc Natl Acad Sci U S A, 111, E2831. PubMed id: 24982189 DOI: 10.1073/pnas.1402926111

Date:

11-Jun-14 Release date: 09-Jul-14

Protein chains

Q9U2D9  (GYS_CAEEL) -  Glycogen [starch] synthase from Caenorhabditis elegans

Seq: 672 a.a.

Struc: 650 a.a.

Protein chains

H2KYQ5  (GYG1_CAEEL) -  Glycogenin-1 from Caenorhabditis elegans

Seq: 429 a.a.

Struc: 34 a.a.

Protein chain

H2KYQ5  (GYG1_CAEEL) -  Glycogenin-1 from Caenorhabditis elegans

Seq: 429 a.a.

Struc: 33 a.a.

Protein chain

H2KYQ5  (GYG1_CAEEL) -  Glycogenin-1 from Caenorhabditis elegans

Seq: 429 a.a.

Struc: 35 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, C, D, B: E.C.2.4.1.11 - glycogen(starch) synthase.
• Pathway: Glycogen
• Reaction: [(1->4)-alpha-D-glucosyl](n) + UDP-alpha-D-glucose = [(1->4)-alpha-D- glucosyl](n+1) + UDP + H⁺
• Enzyme class 2: Chains G, E, H, F: E.C.2.4.1.186 - glycogenin glucosyltransferase.
• Reaction:
  1. L-tyrosyl-[glycogenin] + UDP-alpha-D-glucose = alpha-D-glucosyl-L- tyrosyl-[glycogenin] + UDP + H⁺
  2. [1,4-alpha-D-glucosyl](n)-L-tyrosyl-[glycogenin] + UDP-alpha-D- glucose = [1,4-alpha-D-glucosyl](n+1)-L-tyrosyl-[glycogenin] + UDP + H⁺
• Cofactor: Mn(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.1402926111

Proc Natl Acad Sci U S A 111:E2831 (2014)

PubMed id: 24982189

Structural basis for the recruitment of glycogen synthase by glycogenin.

E.Zeqiraj, X.Tang, R.W.Hunter, M.García-Rocha, A.Judd, M.Deak, A.von Wilamowitz-Moellendorff, I.Kurinov, J.J.Guinovart, M.Tyers, K.Sakamoto, F.Sicheri.

ABSTRACT

Glycogen is a primary form of energy storage in eukaryotes that is essential for glucose homeostasis. The glycogen polymer is synthesized from glucose through the cooperative action of glycogen synthase (GS), glycogenin (GN), and glycogen branching enzyme and forms particles that range in size from 10 to 290 nm. GS is regulated by allosteric activation upon glucose-6-phosphate binding and inactivation by phosphorylation on its N- and C-terminal regulatory tails. GS alone is incapable of starting synthesis of a glycogen particle de novo, but instead it extends preexisting chains initiated by glycogenin. The molecular determinants by which GS recognizes self-glucosylated GN, the first step in glycogenesis, are unknown. We describe the crystal structure of Caenorhabditis elegans GS in complex with a minimal GS targeting sequence in GN and show that a 34-residue region of GN binds to a conserved surface on GS that is distinct from previously characterized allosteric and binding surfaces on the enzyme. The interaction identified in the GS-GN costructure is required for GS-GN interaction and for glycogen synthesis in a cell-free system and in intact cells. The interaction of full-length GS-GN proteins is enhanced by an avidity effect imparted by a dimeric state of GN and a tetrameric state of GS. Finally, the structure of the N- and C-terminal regulatory tails of GS provide a basis for understanding phosphoregulation of glycogen synthesis. These results uncover a central molecular mechanism that governs glycogen metabolism.