spacer
spacer

PDBsum entry 2gm1
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Cell cycle PDB id
2gm1

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
328 a.a. *
Ligands
2AZ ×4
ADP ×4
Metals
_MG ×8
Waters ×236
* Residue conservation analysis
PDB id:
2gm1
Name: Cell cycle
Title: Crystal structure of the mitotic kinesin eg5 in complex with mg-adp and n-(3-aminopropyl)-n-((3-benzyl-5-chloro-4-oxo-3,4- dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)(cyclopropyl)methyl)-4- methylbenzamide
Structure: Kinesin-related motor protein eg5. Chain: a, b, d, e. Fragment: residues 1-368. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: eg5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.30Å     R-factor:   0.230     R-free:   0.269
Authors: S.Sheriff
Key ref: K.S.Kim et al. (2006). Synthesis and SAR of pyrrolotriazine-4-one based Eg5 inhibitors. Bioorg Med Chem Lett, 16, 3937-3942. PubMed id: 16730979 DOI: 10.1016/j.bmcl.2006.05.037
Date:
05-Apr-06     Release date:   27-Jun-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.
328 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.2006.05.037 Bioorg Med Chem Lett 16:3937-3942 (2006)
PubMed id: 16730979  
 
 
Synthesis and SAR of pyrrolotriazine-4-one based Eg5 inhibitors.
K.S.Kim, S.Lu, L.A.Cornelius, L.J.Lombardo, R.M.Borzilleri, G.M.Schroeder, C.Sheng, G.Rovnyak, D.Crews, R.J.Schmidt, D.K.Williams, R.S.Bhide, S.C.Traeger, P.A.McDonnell, L.Mueller, S.Sheriff, J.A.Newitt, A.T.Pudzianowski, Z.Yang, R.Wild, F.Y.Lee, R.Batorsky, J.S.Ryder, M.Ortega-Nanos, H.Shen, M.Gottardis, D.L.Roussell.
 
  ABSTRACT  
 
Synthesis and SAR of substituted pyrrolotriazine-4-one analogues as Eg5 inhibitors are described. Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays. In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22993085 S.K.Talapatra, A.W.Schüttelkopf, and F.Kozielski (2012).
The structure of the ternary Eg5-ADP-ispinesib complex.
  Acta Crystallogr D Biol Crystallogr, 68, 1311-1319.
PDB code: 4ap0
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.  
18467094 X.Teng, H.Keys, J.Yuan, A.Degterev, and G.D.Cuny (2008).
Structure-activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors.
  Bioorg Med Chem Lett, 18, 3219-3223.  
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
17062577 T.C.Krzysiak, and S.P.Gilbert (2006).
Dimeric Eg5 maintains processivity through alternating-site catalysis with rate-limiting ATP hydrolysis.
  J Biol Chem, 281, 39444-39454.  
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