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PDBsum entry 3daj
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protein ligands links
Transferase PDB id
3daj

 

 

 

 

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Contents
Protein chain
245 a.a. *
Ligands
FXG
Waters ×100
* Residue conservation analysis
PDB id:
3daj
Name: Transferase
Title: Crystal structure of aurora a complexed with an inhibitor discovered through site-directed dynamic tethering
Structure: Serine/threonine kinase 6. Chain: a. Synonym: aurora-a. Engineered: yes. Mutation: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: aurka, stk6. Expressed in: escherichia coli
Resolution:
2.00Å     R-factor:   0.253     R-free:   0.284
Authors: M.M.He
Key ref: M.T.Cancilla et al. (2008). Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry. Bioorg Med Chem Lett, 18, 3978-3981. PubMed id: 18579375 DOI: 10.1016/j.bmcl.2008.06.011
Date:
29-May-08     Release date:   08-Jul-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P97477  (AURKA_MOUSE) -  Aurora kinase A from Mus musculus
Seq:
Struc: 		395 a.a.
245 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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    
 
 
DOI no: 10.1016/j.bmcl.2008.06.011 Bioorg Med Chem Lett 18:3978-3981 (2008)
PubMed id: 18579375  
 
 
Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry.
M.T.Cancilla, M.M.He, N.Viswanathan, R.L.Simmons, M.Taylor, A.D.Fung, K.Cao, D.A.Erlanson.
 
  ABSTRACT  
 
We demonstrate a fragment-based lead discovery method that combines site-directed ligand discovery with dynamic combinatorial chemistry. Our technique targets dynamic combinatorial screening to a specified region of a protein by using reversible disulfide chemistry. We have used this technology to rapidly identify inhibitors of the drug target Aurora A that span the purine-binding site and the adaptive pocket of the kinase. The binding mode of a noncovalent inhibitor has been further characterized through crystallography.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21459573 D.A.Erlanson, J.W.Arndt, M.T.Cancilla, K.Cao, R.A.Elling, N.English, J.Friedman, S.K.Hansen, C.Hession, I.Joseph, G.Kumaravel, W.C.Lee, K.E.Lind, R.S.McDowell, K.Miatkowski, C.Nguyen, T.B.Nguyen, S.Park, N.Pathan, D.M.Penny, M.J.Romanowski, D.Scott, L.Silvian, R.L.Simmons, B.T.Tangonan, W.Yang, and L.Sun (2011).
Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.
  Bioorg Med Chem Lett, 21, 3078-3083.
PDB codes: 3pwy 3qc4
  21337433 M.Capela, N.J.Mosey, L.Xing, R.Wang, and A.Petitjean (2011).
Amine exchange in formamidines: an experimental and theoretical study.
  Chemistry, 17, 4598-4612.  
21104718 L.Azéma, K.Bathany, and B.Rayner (2010).
2'-O-Appended polyamines that increase triple-helix-forming oligonucleotide affinity are selected by dynamic combinatorial chemistry.
  Chembiochem, 11, 2513-2516.  
20848037 L.He, Y.Jiang, C.Tu, G.Li, B.Zhu, C.Jin, Q.Zhu, D.Yan, and X.Zhu (2010).
Self-assembled encapsulation systems with pH tunable release property based on reversible covalent bond.
  Chem Commun (Camb), 46, 7569-7571.  
20448900 P.Besenius, P.A.Cormack, R.F.Ludlow, S.Otto, and D.C.Sherrington (2010).
Affinity chromatography in dynamic combinatorial libraries: one-pot amplification and isolation of a strongly binding receptor.
  Org Biomol Chem, 8, 2414-2418.  
20544774 R.Caraballo, M.Sakulsombat, and O.Ramström (2010).
Towards dynamic drug design: identification and optimization of beta-galactosidase inhibitors from a dynamic hemithioacetal system.
  Chembiochem, 11, 1600-1606.  
19827080 D.E.Scott, G.J.Dawes, M.Ando, C.Abell, and A.Ciulli (2009).
A fragment-based approach to probing adenosine recognition sites by using dynamic combinatorial chemistry.
  Chembiochem, 10, 2772-2779.
PDB codes: 3iob 3ioc 3iod 3ioe
19679363 M.F.Schmidt, and J.Rademann (2009).
Dynamic template-assisted strategies in fragment-based drug discovery.
  Trends Biotechnol, 27, 512-521.  
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 codes are shown on the right.

 

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