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PDBsum entry 3f88
Go to PDB code: 
protein ligands links
Transferase PDB id
3f88

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
341 a.a. *
Ligands
3HT ×2
2HT ×2
Waters ×145
* Residue conservation analysis
PDB id:
3f88
Name: Transferase
Title: Glycogen synthase kinase 3beta inhibitor complex
Structure: Glycogen synthase kinase-3 beta. Chain: a, b. Fragment: unp residues 35-383, protein kinase domain. Synonym: gsk-3 beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gsk3b. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.60Å     R-factor:   0.204     R-free:   0.281
Authors: C.D.Mol,D.R.Dougan
Key ref: M.Saitoh et al. (2009). Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta. Bioorg Med Chem Lett, 17, 2017-2029. PubMed id: 19200745
Date:
11-Nov-08     Release date:   10-Mar-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P49841  (GSK3B_HUMAN) -  Glycogen synthase kinase-3 beta from Homo sapiens
Seq:
Struc: 		420 a.a.
341 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.2.7.11.1  - non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
 + ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
 + ADP
 + H(+)
   Enzyme class 2: E.C.2.7.11.26  - [tau protein] kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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+
L-seryl-[tau protein]
 + ATP
 = O-phospho-L-seryl-[tau protein]
 + ADP
 + H(+)
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    
 
 
Bioorg Med Chem Lett 17:2017-2029 (2009)
PubMed id: 19200745  
 
 
Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
M.Saitoh, J.Kunitomo, E.Kimura, Y.Hayase, H.Kobayashi, N.Uchiyama, T.Kawamoto, T.Tanaka, C.D.Mol, D.R.Dougan, G.S.Textor, G.P.Snell, F.Itoh.
 
  ABSTRACT  
 
Glycogen synthase kinase-3beta (GSK-3beta) is implicated in abnormal hyperphosphorylation of tau protein and its inhibitors are expected to be a promising therapeutic agents for the treatment of Alzheimer's disease. Here we report design, synthesis and structure-activity relationships of a novel series of oxadiazole derivatives as GSK-3beta inhibitors. Among these inhibitors, compound 20x showed highly selective and potent GSK-3beta inhibitory activity in vitro and its binding mode was determined by obtaining the X-ray co-crystal structure of 20x and GSK-3beta.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20821241 G.E.Atilla-Gokcumen, L.Di Costanzo, and E.Meggers (2011).
Structure of anticancer ruthenium half-sandwich complex bound to glycogen synthase kinase 3β.
  J Biol Inorg Chem, 16, 45-50.
PDB code: 3m1s
21212533 K.Saeki, M.Machida, Y.Kinoshita, R.Takasawa, and S.Tanuma (2011).
Glycogen synthase kinase-3β2 has lower phosphorylation activity to tau than glycogen synthase kinase-3β1.
  Biol Pharm Bull, 34, 146-149.  
  21469159 S.Y.Lu, Y.J.Jiang, J.Lv, J.W.Zou, and T.X.Wu (2011).
Role of bridging water molecules in GSK3β-inhibitor complexes: insights from QM/MM, MD, and molecular docking studies.
  J Comput Chem, 32, 1907-1918.  
21105670 I.Buch, D.Fishelovitch, N.London, B.Raveh, H.J.Wolfson, and R.Nussinov (2010).
Allosteric regulation of glycogen synthase kinase 3β: a theoretical study.
  Biochemistry, 49, 10890-10901.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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