PDBsum entry 1pmv

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Transferase PDB id
Protein chain
347 a.a. *
Waters ×100
* Residue conservation analysis
PDB id:
Name: Transferase
Title: The structure of jnk3 in complex with a dihydroanthrapyrazole inhibitor
Structure: Mitogen-activated protein kinase 10. Chain: a. Synonym: stress-activated protein kinase jnk3, c-jun n- terminal kinase 3, map kinase p49 3f12. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mk10_human. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.50Å     R-factor:   0.222     R-free:   0.282
Authors: G.Scapin,S.B.Patel,J.Lisnock,J.W.Becker,P.V.Lograsso
Key ref:
G.Scapin et al. (2003). The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. Chem Biol, 10, 705-712. PubMed id: 12954329 DOI: 10.1016/S1074-5521(03)00159-5
11-Jun-03     Release date:   09-Sep-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P53779  (MK10_HUMAN) -  Mitogen-activated protein kinase 10
464 a.a.
347 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ 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  


DOI no: 10.1016/S1074-5521(03)00159-5 Chem Biol 10:705-712 (2003)
PubMed id: 12954329  
The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity.
G.Scapin, S.B.Patel, J.Lisnock, J.W.Becker, P.V.LoGrasso.
The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.
  Selected figure(s)  
Figure 1.
Figure 1. Schematic Representation of the ATP Binding Site in KinasesATP (in ball-and-sticks) interacts mainly with the linker/adenine binding region (1), the ribose binding region (2), and the phosphate binding region (3). The two hydrophobic regions I (4) and II (5) do not directly interact with ATP and contain residues that vary among kinases, thus providing possibilities for the development of selective inhibitors [17]. Figures 1, 2B, and 3–6 were made with RIBBONS [42].
Figure 5.
Figure 5. Binding of Compound 3 to JNK3(A) Overlay of the Cα traces of JNK3:compound 1 (magenta) and JNK3:compound 3 complexes (yellow) in the region of the glycine-rich loop (G71-V78). The conformational change observed for residues Ile70–Ile77 was ligand induced.(B) Close-up of the compound 3 binding site; hydrogen bond interactions with protein atoms are shown as blue dotted lines.
  The above figures are reprinted by permission from Cell Press: Chem Biol (2003, 10, 705-712) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20393763 B.V.Kumar, R.Kotla, R.Buddiga, J.Roy, S.S.Singh, R.Gundla, M.Ravikumar, and J.A.Sarma (2011).
Ligand-based and structure-based approaches in identifying ideal pharmacophore against c-Jun N-terminal kinase-3.
  J Mol Model, 17, 151-163.  
19942586 D.Huang, T.Zhou, K.Lafleur, C.Nevado, and A.Caflisch (2010).
Kinase selectivity potential for inhibitors targeting the ATP binding site: a network analysis.
  Bioinformatics, 26, 198-204.  
21108268 M.Goettert, V.Schattel, P.Koch, I.Merfort, and S.Laufer (2010).
Biological evaluation and structural determinants of p38α mitogen-activated-protein kinase and c-Jun-N-terminal kinase 3 inhibition by flavonoids.
  Chembiochem, 11, 2579-2588.  
19947601 T.Kamenecka, R.Jiang, X.Song, D.Duckett, W.Chen, Y.Y.Ling, J.Habel, J.D.Laughlin, J.Chambers, M.Figuera-Losada, M.D.Cameron, L.Lin, C.H.Ruiz, and P.V.LoGrasso (2010).
Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.
  J Med Chem, 53, 419-431.
PDB code: 3kvx
19519745 F.Robert, C.Williams, Y.Yan, E.Donohue, R.Cencic, S.K.Burley, and J.Pelletier (2009).
Blocking UV-induced eIF2alpha phosphorylation with small molecule inhibitors of GCN2.
  Chem Biol Drug Des, 74, 57-67.  
19261605 T.Kamenecka, J.Habel, D.Duckett, W.Chen, Y.Y.Ling, B.Frackowiak, R.Jiang, Y.Shin, X.Song, and P.Lograsso (2009).
Structure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) over p38.
  J Biol Chem, 284, 12853-12861.
PDB codes: 3fi2 3fi3
19015641 Z.Tang, S.Jiang, R.Du, E.T.Petri, A.El-Telbany, P.S.Chan, T.Kijima, S.Dietrich, K.Matsui, M.Kobayashi, S.Sasada, N.Okamoto, H.Suzuki, K.Kawahara, T.Iwasaki, K.Nakagawa, I.Kawase, J.G.Christensen, T.Hirashima, B.Halmos, R.Salgia, T.J.Boggon, J.A.Kern, and P.C.Ma (2009).
Disruption of the EGFR E884-R958 ion pair conserved in the human kinome differentially alters signaling and inhibitor sensitivity.
  Oncogene, 28, 518-533.  
18480048 M.L.Chu, L.M.Chavas, K.T.Douglas, P.A.Eyers, and L.Tabernero (2008).
Crystal structure of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125.
  J Biol Chem, 283, 21495-21500.
PDB codes: 2zmc 2zmd
17164528 C.W.Chung (2007).
The use of biophysical methods increases success in obtaining liganded crystal structures.
  Acta Crystallogr D Biol Crystallogr, 63, 62-71.  
17694525 D.Kuhn, N.Weskamp, E.Hüllermeier, and G.Klebe (2007).
Functional Classification of Protein Kinase Binding Sites Using Cavbase.
  ChemMedChem, 2, 1432-1447.  
16708364 E.Perola (2006).
Minimizing false positives in kinase virtual screens.
  Proteins, 64, 422-435.  
17158707 M.A.Bogoyevitch, and B.Kobe (2006).
Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases.
  Microbiol Mol Biol Rev, 70, 1061-1095.  
17038480 S.E.Sweeney, and G.S.Firestein (2006).
Mitogen activated protein kinase inhibitors: where are we now and where are we going?
  Ann Rheum Dis, 65, iii83-iii88.  
15882611 M.A.Bogoyevitch (2005).
Therapeutic promise of JNK ATP-noncompetitive inhibitors.
  Trends Mol Med, 11, 232-239.  
15673436 S.Brecht, R.Kirchhof, A.Chromik, M.Willesen, T.Nicolaus, G.Raivich, J.Wessig, V.Waetzig, M.Goetz, M.Claussen, D.Pearse, C.Y.Kuan, E.Vaudano, A.Behrens, E.Wagner, R.A.Flavell, R.J.Davis, and T.Herdegen (2005).
Specific pathophysiological functions of JNK isoforms in the brain.
  Eur J Neurosci, 21, 363-377.  
15501728 L.Resnick, and M.Fennell (2004).
Targeting JNK3 for the treatment of neurodegenerative disorders.
  Drug Discov Today, 9, 932-939.  
15141161 Y.S.Heo, S.K.Kim, C.I.Seo, Y.K.Kim, B.J.Sung, H.S.Lee, J.I.Lee, S.Y.Park, J.H.Kim, K.Y.Hwang, Y.L.Hyun, Y.H.Jeon, S.Ro, J.M.Cho, T.G.Lee, and C.H.Yang (2004).
Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125.
  EMBO J, 23, 2185-2195.
PDB codes: 1ukh 1uki
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.