PDBsum entry 1gng

Transferase

PDB id: 1gng

Contents

Protein chains

350 a.a. *

26 a.a. *

Ligands

SO4 ×4

TRS

Waters ×140

* Residue conservation analysis

PDB id:

1gng

Name:

Transferase

Title:

Glycogen synthase kinase-3 beta (gsk3) complex with frattide peptide

Structure:

Glycogen synthase kinase-3 beta. Chain: a, b. Fragment: residues 27-393. Synonym: gsk3b. Engineered: yes. Frattide. Chain: x, y. Fragment: residues 188-226. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Organism_taxid: 9606

Biol. unit:

Dimer (from PDB file)

Resolution:

2.60Å R-factor: 0.196 R-free: 0.262

Authors:

B.Bax,P.S.Carter,C.Lewis,A.R.Guy,A.Bridges,R.Tanner,G.Pettman, C.Mannix,A.A.Culbert,M.J.B.Brown,D.G.Smith,A.D.Reith

Key ref:

B.Bax et al. (2001). The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure, 9, 1143-1152. PubMed id: 11738041 DOI: 10.1016/S0969-2126(01)00679-7

Date:

04-Oct-01 Release date: 03-Oct-02

Protein chains

P49841  (GSK3B_HUMAN) -  Glycogen synthase kinase-3 beta from Homo sapiens

Seq: 420 a.a.

Struc: 350 a.a.

Protein chains

Q92837  (FRAT1_HUMAN) -  Proto-oncogene FRAT1 from Homo sapiens

Seq: 279 a.a.

Struc: 26 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺
• Enzyme class 2: Chains A, B: E.C.2.7.11.26 - [tau protein] kinase.
• Reaction:
  1. L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H⁺
  2. L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H⁺

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: 10.1016/S0969-2126(01)00679-7

Structure 9:1143-1152 (2001)

PubMed id: 11738041

The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation.

B.Bax, P.S.Carter, C.Lewis, A.R.Guy, A.Bridges, R.Tanner, G.Pettman, C.Mannix, A.A.Culbert, M.J.Brown, D.G.Smith, A.D.Reith.

ABSTRACT

BACKGROUND: Glycogen synthase kinase-3 (GSK-3) sequentially phosphorylates four serine residues on glycogen synthase (GS), in the sequence SxxxSxxxSxxx-SxxxS(p), by recognizing and phosphorylating the first serine in the sequence motif SxxxS(P) (where S(p) represents a phosphoserine). FRATtide (a peptide derived from a GSK-3 binding protein) binds to GSK-3 and blocks GSK-3 from interacting with Axin. This inhibits the Axin-dependent phosphorylation of beta-catenin by GSK-3. RESULTS: Structures of uncomplexed Tyr216 phosphorylated GSK-3beta and of its complex with a peptide and a sulfate ion both show the activation loop adopting a conformation similar to that in the phosphorylated and active forms of the related kinases CDK2 and ERK2. The sulfate ion, adjacent to Val214 on the activation loop, represents the binding site for the phosphoserine residue on 'primed' substrates. The peptide FRATtide forms a helix-turn-helix motif in binding to the C-terminal lobe of the kinase domain; the FRATtide binding site is close to, but does not obstruct, the substrate binding channel of GSK-3. FRATtide (and FRAT1) does not inhibit the activity of GSK-3 toward GS. CONCLUSIONS: The Axin binding site on GSK-3 presumably overlaps with that for FRATtide; its proximity to the active site explains how Axin may act as a scaffold protein promoting beta-catenin phosphorylation. Tyrosine 216 phosphorylation can induce an active conformation in the activation loop. Pre-phosphorylated substrate peptides can be modeled into the active site of the enzyme, with the P1 residue occupying a pocket partially formed by phosphotyrosine 216 and the P4 phosphoserine occupying the 'primed' binding site.

Selected figure(s)

Figure 2.
Figure 2. The Activation Loop and Substrate Binding(a) The structure of CDK2 (red) with a substrate peptide (purple) and a nonhydrolizable analog of ATP (labeled ATP; only the terminal phosphate group is visible; PDB code 1QMZ; [28]). Ser 5 is the phosphorylatable serine in the substrate. Lysine 8 from the substrate peptide interacts with phosphothreonine 160.(b) Superposed structures of CDK2 (red), ERK2 (yellow; PDB code 2ERK; [27]) and GSK-3 (green; FS crystal form). The sulfate in GSK-3 is labeled and superposes on phosphothreonine residues in CDK2 and ERK2.(c) Coordinates of GSK-3 (green) are shown with a substrate peptide (blue) modeled in the active site. The peptide has been modeled on the peptide in the CDK2 crystal structure (a) with the phosphothreonine residue at position 9 modeled with its phosphate group occupying the position occupied by the sulfate in the crystal structure of the FS crystal form of GSK-3. The figure was drawn with GRASP [47].

The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 1143-1152) copyright 2001.

Figure was selected by the author.