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PDBsum entry 1ogu
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1ogu

 

 

 

 

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Contents
Protein chains
297 a.a. *
253 a.a. *
273 a.a. *
Ligands
ST8 ×2
SGM ×2
Waters ×134
* Residue conservation analysis
PDB id:
1ogu
Name: Transferase
Title: Structure of human thr160-phospho cdk2/cyclin a complexed with a 2- arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitor
Structure: Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Other_details: phosphorylated on thr160. Cyclin a2. Chain: b, d. Fragment: residues 174-432. Synonym: cyclin a, cyclin a3.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.201     R-free:   0.260
Authors: D.J.Pratt,J.A.Endicott,M.E.M.Noble
Key ref: K.L.Sayle et al. (2003). Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2. Bioorg Med Chem Lett, 13, 3079-3082. PubMed id: 12941338 DOI: 10.1016/S0960-894X(03)00651-6
Date:
13-May-03     Release date:   02-Sep-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2 from Homo sapiens
Seq:
Struc: 		298 a.a.
297 a.a.*
Protein chains
Pfam   ArchSchema ?
P20248  (CCNA2_HUMAN) -  Cyclin-A2 from Homo sapiens
Seq:
Struc: 		432 a.a.
253 a.a.
Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2 from Homo sapiens
Seq:
Struc: 		298 a.a.
273 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, C: E.C.2.7.11.22  - cyclin-dependent 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/S0960-894X(03)00651-6 Bioorg Med Chem Lett 13:3079-3082 (2003)
PubMed id: 12941338  
 
 
Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2.
K.L.Sayle, J.Bentley, F.T.Boyle, A.H.Calvert, Y.Cheng, N.J.Curtin, J.A.Endicott, B.T.Golding, I.R.Hardcastle, P.Jewsbury, V.Mesguiche, D.R.Newell, M.E.Noble, R.J.Parsons, D.J.Pratt, L.Z.Wang, R.J.Griffin.
 
  ABSTRACT  
 
A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21286784 P.Dobeš, J.Fanfrlík, J.Rezáč, M.Otyepka, and P.Hobza (2011).
Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors.
  J Comput Aided Mol Des, 25, 223-235.  
18794885 C.Garcia-Echeverria, and W.R.Sellers (2008).
Drug discovery approaches targeting the PI3K/Akt pathway in cancer.
  Oncogene, 27, 5511-5526.  
17571187 F.Marchetti, K.L.Sayle, J.Bentley, W.Clegg, N.J.Curtin, J.A.Endicott, B.T.Golding, R.J.Griffin, K.Haggerty, R.W.Harrington, V.Mesguiche, D.R.Newell, M.E.Noble, R.J.Parsons, D.J.Pratt, L.Z.Wang, and I.R.Hardcastle (2007).
Structure-based design of 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinase 2.
  Org Biomol Chem, 5, 1577-1585.  
16374623 A.T.García-Sosa, and R.L.Mancera (2006).
The effect of a tightly bound water molecule on scaffold diversity in the computer-aided de novo ligand design of CDK2 inhibitors.
  J Mol Model, 12, 422-431.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
15772071 R.I.Feldman, J.M.Wu, M.A.Polokoff, M.J.Kochanny, H.Dinter, D.Zhu, S.L.Biroc, B.Alicke, J.Bryant, S.Yuan, B.O.Buckman, D.Lentz, M.Ferrer, M.Whitlow, M.Adler, S.Finster, Z.Chang, and D.O.Arnaiz (2005).
Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.
  J Biol Chem, 280, 19867-19874.
PDB code: 1z5m
15505811 H.Park, M.S.Yeom, and S.Lee (2004).
Loop flexibility and solvent dynamics as determinants for the selective inhibition of cyclin-dependent kinase 4: comparative molecular dynamics simulation studies of CDK2 and CDK4.
  Chembiochem, 5, 1662-1672.  
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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