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PDBsum entry 2obj
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protein ligands links
Transferase PDB id
2obj

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
273 a.a. *
Ligands
VRV
Waters ×68
* Residue conservation analysis
PDB id:
2obj
Name: Transferase
Title: Crystal structure of human pim-1 kinase in complex with inhibitor
Structure: Proto-oncogene serine/threonine-protein kinase pim-1. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.50Å     R-factor:   0.205     R-free:   0.246
Authors: N.Yao,I.W.Cheney,S.Yan
Key ref: I.W.Cheney et al. (2007). Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase. Bioorg Med Chem Lett, 17, 1679-1683. PubMed id: 17251021
Date:
19-Dec-06     Release date:   06-Feb-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11309  (PIM1_HUMAN) -  Serine/threonine-protein kinase pim-1 from Homo sapiens
Seq:
Struc: 		313 a.a.
273 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Bioorg Med Chem Lett 17:1679-1683 (2007)
PubMed id: 17251021  
 
 
Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase.
I.W.Cheney, S.Yan, T.Appleby, H.Walker, T.Vo, N.Yao, R.Hamatake, Z.Hong, J.Z.Wu.
 
  ABSTRACT  
 
A novel series of highly potent substituted pyridone Pim-1 kinase inhibitors is described. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with the most potent Pim-1 inhibitor reported (IC(50)=50 nM). A hydrogen bond matrix involving the Pim-1 inhibitor, two water molecules, and the catalytic core, together with a potential weak hydrogen bond between an aromatic hydrogen on the R(1) phenyl ring and a main-chain carbonyl of Pim-1, accounts for the overall potency of this inhibitor.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22719473 M.S.Al-Said, M.M.Ghorab, H.A.Ghabbour, S.Arshad, and H.K.Fun (2012).
1-(3-Ethyl-phen-yl)-4,6-dimethyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile.
  Acta Crystallogr Sect E Struct Rep Online, 68, o1679.  
21062737 D.Morishita, M.Takami, S.Yoshikawa, R.Katayama, S.Sato, M.Kukimoto-Niino, T.Umehara, M.Shirouzu, K.Sekimizu, S.Yokoyama, and N.Fujita (2011).
Cell-permeable carboxyl-terminal p27(Kip1) peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase.
  J Biol Chem, 286, 2681-2688.
PDB code: 3a99
21507633 Y.Xiang, B.Hirth, G.Asmussen, H.P.Biemann, K.A.Bishop, A.Good, M.Fitzgerald, T.Gladysheva, A.Jain, K.Jancsics, J.Liu, M.Metz, A.Papoulis, R.Skerlj, J.D.Stepp, and R.R.Wei (2011).
The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.
  Bioorg Med Chem Lett, 21, 3050-3056.
PDB codes: 3r00 3r01 3r02 3r04
  20145274 L.Brault, C.Gasser, F.Bracher, K.Huber, S.Knapp, and J.Schwaller (2010).
PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers.
  Haematologica, 95, 1004-1015.  
20919829 N.S.Magnuson, Z.Wang, G.Ding, and R.Reeves (2010).
Why target PIM1 for cancer diagnosis and treatment?
  Future Oncol, 6, 1461-1478.  
19934869 J.Stumpner, A.Redel, A.Kellermann, C.A.Lotz, C.A.Blomeyer, T.M.Smul, F.Kehl, N.Roewer, and M.Lange (2009).
Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction.
  Anesthesiology, 111, 1257-1264.  
19825806 S.M.Mumenthaler, P.Y.Ng, A.Hodge, D.Bearss, G.Berk, S.Kanekal, S.Redkar, P.Taverna, D.B.Agus, and A.Jain (2009).
Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes.
  Mol Cancer Ther, 8, 2882-2893.  
17920279 T.Crabbe, M.J.Welham, and S.G.Ward (2007).
The PI3K inhibitor arsenal: choose your weapon!
  Trends Biochem Sci, 32, 450-456.  
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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