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PDBsum entry 2c6d
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protein ligands links
Transferase PDB id
2c6d

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
255 a.a. *
Ligands
GOL
PO4
ANP
Waters ×156
* Residue conservation analysis
PDB id:
2c6d
Name: Transferase
Title: Aurora a kinase activated mutant (t287d) in complex with adpnp
Structure: Serine/threonine-protein kinase 6. Chain: a. Fragment: catalytic kinase domain residues 124-398. Synonym: aurora a kinase. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.20Å     R-factor:   0.230     R-free:   0.280
Authors: R.A.Pauptit,A.D.Pannifer,J.Breed,H.H.J.Mcmiken,S.Rowsell,M.Anderson
Key ref: N.M.Heron et al. (2006). SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors. Bioorg Med Chem Lett, 16, 1320-1323. PubMed id: 16337122 DOI: 10.1016/j.bmcl.2005.11.053
Date:
09-Nov-05     Release date:   11-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O14965  (AURKA_HUMAN) -  Aurora kinase A from Homo sapiens
Seq:
Struc: 		403 a.a.
255 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]
Bound ligand (Het Group name = ANP)
matches with 92.86% similarity 		+ ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
Bound ligand (Het Group name = ANP)
matches with 92.86% similarity 		+ ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2005.11.053 Bioorg Med Chem Lett 16:1320-1323 (2006)
PubMed id: 16337122  
 
 
SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors.
N.M.Heron, M.Anderson, D.P.Blowers, J.Breed, J.M.Eden, S.Green, G.B.Hill, T.Johnson, F.H.Jung, H.H.McMiken, A.A.Mortlock, A.D.Pannifer, R.A.Pauptit, J.Pink, N.J.Roberts, S.Rowsell.
 
  ABSTRACT  
 
A novel series of 5-aminopyrimidinyl quinazolines has been developed from anilino-quinazoline 1, which was identified in a high throughput screen for Aurora A. Introduction of the pyrimidine ring and optimisation of the substituents both on this ring and at the C7 position of the quinazoline led to the discovery of compounds that are highly specific Aurora kinase inhibitors. Co-crystallisation of one of these inhibitors with a fragment of Aurora A shows the importance of the benzamido group in achieving selectivity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21147253 A.Yan, L.Wang, S.Xu, and J.Xu (2011).
Aurora-A kinase inhibitor scaffolds and binding modes.
  Drug Discov Today, 16, 260-269.  
20067443 C.A.Dodson, M.Kosmopoulou, M.W.Richards, B.Atrash, V.Bavetsias, J.Blagg, and R.Bayliss (2010).
Crystal structure of an Aurora-A mutant that mimics Aurora-B bound to MLN8054: insights into selectivity and drug design.
  Biochem J, 427, 19-28.
PDB codes: 2wtv 2wtw
19582900 D.Demidov, S.Hesse, A.Tewes, T.Rutten, J.Fuchs, R.K.Ashtiyani, S.Lein, A.Fischer, G.Reuter, and A.Houben (2009).
Aurora1 phosphorylation activity on histone H3 and its cross-talk with other post-translational histone modifications in Arabidopsis.
  Plant J, 59, 221-230.  
19320832 N.Jetton, K.G.Rothberg, J.G.Hubbard, J.Wise, Y.Li, H.L.Ball, and L.Ruben (2009).
The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms.
  Mol Microbiol, 72, 442-458.  
19359241 P.J.Scutt, M.L.Chu, D.A.Sloane, M.Cherry, C.R.Bignell, D.H.Williams, and P.A.Eyers (2009).
Discovery and exploitation of inhibitor-resistant aurora and polo kinase mutants for the analysis of mitotic networks.
  J Biol Chem, 284, 15880-15893.  
19339067 R.L.van Montfort, and P.Workman (2009).
Structure-based design of molecular cancer therapeutics.
  Trends Biotechnol, 27, 315-328.  
18940662 A.C.Dar, M.S.Lopez, and K.M.Shokat (2008).
Small molecule recognition of c-Src via the Imatinib-binding conformation.
  Chem Biol, 15, 1015-1022.
PDB codes: 3el7 3el8
18267130 B.D.Marsden, and S.Knapp (2008).
Doing more than just the structure-structural genomics in kinase drug discovery.
  Curr Opin Chem Biol, 12, 40-45.  
18493651 B.G.Perera, and D.J.Maly (2008).
Design, synthesis and characterization of "clickable" 4-anilinoquinazoline kinase inhibitors.
  Mol Biosyst, 4, 542-550.  
18662907 B.Zhao, A.Smallwood, J.Yang, K.Koretke, K.Nurse, A.Calamari, R.B.Kirkpatrick, and Z.Lai (2008).
Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2.
  Protein Sci, 17, 1791-1797.
PDB code: 3e5a
18404149 D.M.Goldstein, N.S.Gray, and P.P.Zarrinkar (2008).
High-throughput kinase profiling as a platform for drug discovery.
  Nat Rev Drug Discov, 7, 391-397.  
18342020 J.A.Lewis, E.P.Lebois, and C.W.Lindsley (2008).
Allosteric modulation of kinases and GPCRs: design principles and structural diversity.
  Curr Opin Chem Biol, 12, 269-280.  
18405842 W.Muster, A.Breidenbach, H.Fischer, S.Kirchner, L.Müller, and A.Pähler (2008).
Computational toxicology in drug development.
  Drug Discov Today, 13, 303-310.  
17334377 J.A.Blair, D.Rauh, C.Kung, C.H.Yun, Q.W.Fan, H.Rode, C.Zhang, M.J.Eck, W.A.Weiss, and K.M.Shokat (2007).
Structure-guided development of affinity probes for tyrosine kinases using chemical genetics.
  Nat Chem Biol, 3, 229-238.
PDB codes: 2hwo 2hwp 2j5e 2j5f
17541419 M.P.Mazanetz, and P.M.Fischer (2007).
Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases.
  Nat Rev Drug Discov, 6, 464-479.  
16860930 S.K.Bodvarsdottir, H.Hilmarsdottir, V.Birgisdottir, M.Steinarsdottir, J.G.Jonasson, and J.E.Eyfjord (2007).
Aurora-A amplification associated with BRCA2 mutation in breast tumours.
  Cancer Lett, 248, 96.  
16783341 Y.Liu, and N.S.Gray (2006).
Rational design of inhibitors that bind to inactive kinase conformations.
  Nat Chem Biol, 2, 358-364.  
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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