spacer
spacer

PDBsum entry 2fl2
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Cell cycle PDB id
2fl2

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
330 a.a. *
Ligands
ADP ×2
N4T ×2
Metals
_MG ×2
Waters ×129
* Residue conservation analysis
PDB id:
2fl2
Name: Cell cycle
Title: Crystal structure of ksp in complex with inhibitor 19
Structure: Kinesin-like protein kif11. Chain: a, b. Fragment: kinesin-motor domain, residues 1-368. Synonym: kinesin-related motor protein eg5, kinesin-like spindle protein hksp, thyroid receptor interacting protein 5, trip5, kinesin- like protein 1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: kif11, eg5, knsl1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.50Å     R-factor:   0.257     R-free:   0.316
Authors: Y.Yan
Key ref: M.E.Fraley et al. (2006). Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP. Bioorg Med Chem Lett, 16, 1775-1779. PubMed id: 16439123 DOI: 10.1016/j.bmcl.2006.01.030
Date:
05-Jan-06     Release date:   07-Feb-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P52732  (KIF11_HUMAN) -  Kinesin-like protein KIF11 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1056 a.a.
330 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/j.bmcl.2006.01.030 Bioorg Med Chem Lett 16:1775-1779 (2006)
PubMed id: 16439123  
 
 
Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.
M.E.Fraley, R.M.Garbaccio, K.L.Arrington, W.F.Hoffman, E.S.Tasber, P.J.Coleman, C.A.Buser, E.S.Walsh, K.Hamilton, C.Fernandes, M.D.Schaber, R.B.Lobell, W.Tao, V.J.South, Y.Yan, L.C.Kuo, T.Prueksaritanont, C.Shu, M.Torrent, D.C.Heimbrook, N.E.Kohl, H.E.Huber, G.D.Hartman.
 
  ABSTRACT  
 
The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is described. Introduction of basic amide and urea moieties to the dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with EC(50)s<10nM. Ancillary hERG activity was evaluated for this series of inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21382720 B.Babu, M.Lee, L.Lee, R.Strobel, O.Brockway, A.Nickols, R.Sjoholm, S.Tzou, S.Chavda, D.Desta, G.Fraley, A.Siegfried, W.Pennington, R.M.Hartley, C.Westbrook, S.L.Mooberry, K.Kiakos, J.A.Hartley, and M.Lee (2011).
Acetyl analogs of combretastatin A-4: synthesis and biological studies.
  Bioorg Med Chem, 19, 2359-2367.  
20737530 H.Prokopcová, D.Dallinger, G.Uray, H.Y.Kaan, V.Ulaganathan, F.Kozielski, C.Laggner, and C.O.Kappe (2010).
Structure-activity relationships and molecular docking of novel dihydropyrimidine-based mitotic Eg5 inhibitors.
  ChemMedChem, 5, 1760-1769.  
19483335 C.Jiang, Q.You, F.Liu, W.Wu, Q.Guo, J.Chern, L.Yang, and M.Chen (2009).
Design, synthesis and evaluation of tetrahydroisoquinolines as new kinesin spindle protein inhibitors.
  Chem Pharm Bull (Tokyo), 57, 567-571.  
19156502 D.Huszar, M.E.Theoclitou, J.Skolnik, and R.Herbst (2009).
Kinesin motor proteins as targets for cancer therapy.
  Cancer Metastasis Rev, 28, 197-208.  
19545421 S.Valensin, C.Ghiron, C.Lamanna, A.Kremer, M.Rossi, P.Ferruzzi, M.Nievo, and A.Bakker (2009).
KIF11 inhibition for glioblastoma treatment: reason to hope or a struggle with the brain?
  BMC Cancer, 9, 196.  
  19259408 A.L.Jackson, M.Mao, S.Kobayashi, T.Ward, M.Biery, H.Dai, S.R.Bartz, and P.S.Linsley (2008).
Chromosome 20q amplification regulates in vitro response to Kinesin-5 inhibitor.
  Cancer Inform, 6, 147-164.  
17588180 C.Jiang, Y.Chen, X.Wang, and Q.You (2007).
Docking studies on kinesin spindle protein inhibitors: an important cooperative 'minor binding pocket' which increases the binding affinity significantly.
  J Mol Model, 13, 987-992.  
17251189 I.Garcia-Saez, S.DeBonis, R.Lopez, F.Trucco, B.Rousseau, P.Thuéry, and F.Kozielski (2007).
Structure of human Eg5 in complex with a new monastrol-based inhibitor bound in the R configuration.
  J Biol Chem, 282, 9740-9747.
PDB code: 2ieh
17854022 K.L.Arrington, and V.Y.Dudkin (2007).
Novel Inhibitors of Checkpoint Kinase 1.
  ChemMedChem, 2, 1571-1585.  
17014086 J.C.Cochran, T.C.Krzysiak, and S.P.Gilbert (2006).
Pathway of ATP hydrolysis by monomeric kinesin Eg5.
  Biochemistry, 45, 12334-12344.  
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.

 

spacer
spacer