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PDBsum entry 3v3v

Go to PDB code: 
protein ligands metals links
Transferase/transferase inhibitor PDB id
3v3v
Jmol
Contents
Protein chain
351 a.a.
Ligands
PRO-LYS-ARG-PRO-
THR-THR-LEU-ASN-
LEU-PHE
MYU
SO4 ×7
Metals
_CL
Waters ×27
PDB id:
3v3v
Name: Transferase/transferase inhibitor
Title: Structural and functional analysis of quercetagetin, a natur inhibitor
Structure: Mitogen-activated protein kinase 8. Chain: a. Fragment: unp residues 1-363. Synonym: map kinase 8, mapk 8, jnk-46, stress-activated pro kinase 1c, sapk1c, stress-activated protein kinase jnk1, c- terminal kinase 1. Engineered: yes. C-jun-amino-terminal kinase-interacting protein 1 chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk8, jnk1, prkm8, sapk1, sapk1c. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Mus musculus. Mouse.
Resolution:
2.70Å     R-factor:   0.228     R-free:   0.266
Authors: S.Baek,N.J.Kang,G.M.Popowicz,M.Arciniega,S.K.Jung,S.Byun,N.R Y.S.Heo,B.Y.Kim,H.J.Lee,T.A.Holak,M.Augustin,A.M.Bode,R.Hub Z.Dong,K.W.Lee
Key ref: S.Baek et al. (2013). Structural and functional analysis of the natural JNK1 inhibitor quercetagetin. J Mol Biol, 425, 411-423. PubMed id: 23142567
Date:
14-Dec-11     Release date:   05-Dec-12    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P45983  (MK08_HUMAN) -  Mitogen-activated protein kinase 8
Seq:
Struc:
427 a.a.
351 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.24  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+
protein
Bound ligand (Het Group name = PRO)
matches with 50.00% similarity
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
J Mol Biol 425:411-423 (2013)
PubMed id: 23142567  
 
 
Structural and functional analysis of the natural JNK1 inhibitor quercetagetin.
S.Baek, N.J.Kang, G.M.Popowicz, M.Arciniega, S.K.Jung, S.Byun, N.R.Song, Y.S.Heo, B.Y.Kim, H.J.Lee, T.A.Holak, M.Augustin, A.M.Bode, R.Huber, Z.Dong, K.W.Lee.
 
  ABSTRACT  
 
c-Jun NH2-terminal kinases (JNKs) and phosphatidylinositol 3-kinase (PI3-K) play critical roles in chronic diseases such as cancer, type II diabetes, and obesity. We describe here the binding of quercetagetin (3,3',4',5,6,7-hydroxyflavone), related flavonoids, and SP600125 to JNK1 and PI3-K by ATP-competitive and immobilized metal ion affinity-based fluorescence polarization assays and measure the effect of quercetagetin on JNK1 and PI3-K activities. Quercetagetin attenuated the phosphorylation of c-Jun and AKT, suppressed AP-1 and NF-κB promoter activities, and also reduced cell transformation. It attenuated tumor incidence and reduced tumor volumes in a two-stage skin carcinogenesis mouse model. Our crystallographic structure determination data show that quercetagetin binds to the ATP-binding site of JNK1. Notably, the interaction between Lys55, Asp169, and Glu73 of JNK1 and the catechol moiety of quercetagetin reorients the N-terminal lobe of JNK1, thereby improving compatibility of the ligand with its binding site. The results of a theoretical docking study suggest a binding mode of PI3-K with the hydroxyl groups of the catechol moiety forming hydrogen bonds with the side chains of Asp964 and Asp841 in the p110γ catalytic subunit. These interactions could contribute to the high inhibitory activity of quercetagetin against PI3-K. Our study suggests the potential use of quercetagetin in the prevention or therapy of cancer and other chronic diseases.