PDBsum entry 2r3m

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Transferase PDB id
Jmol PyMol
Protein chain
283 a.a. *
Waters ×210
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of cyclin-dependent kinase 2 with inhibitor
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469.
1.70Å     R-factor:   0.187     R-free:   0.216
Authors: T.O.Fischmann,A.W.Hruza,V.M.Madison,J.S.Duca
Key ref: T.O.Fischmann et al. (2008). Structure-guided discovery of cyclin-dependent kinase inhibitors. Biopolymers, 89, 372-379. PubMed id: 17937404 DOI: 10.1002/bip.20868
29-Aug-07     Release date:   22-Jan-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
298 a.a.
282 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cyclin A1-CDK2 complex   19 terms 
  Biological process     regulation of gene silencing   32 terms 
  Biochemical function     nucleotide binding     13 terms  


DOI no: 10.1002/bip.20868 Biopolymers 89:372-379 (2008)
PubMed id: 17937404  
Structure-guided discovery of cyclin-dependent kinase inhibitors.
T.O.Fischmann, A.Hruza, J.S.Duca, L.Ramanathan, T.Mayhood, W.T.Windsor, H.V.Le, T.J.Guzi, M.P.Dwyer, K.Paruch, R.J.Doll, E.Lees, D.Parry, W.Seghezzi, V.Madison.
CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules. Further insight into inhibitor/CDK2 interactions was gained from analysis of additional crystal structures. Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19471858 M.H.Seifert (2009).
Robust optimization of scoring functions for a target class.
  J Comput Aided Mol Des, 23, 633-644.  
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