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PDBsum entry 2r3h

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Transferase PDB id
2r3h
Jmol
Contents
Protein chain
292 a.a. *
Ligands
SCE
Waters ×207
* Residue conservation analysis
PDB id:
2r3h
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.
Resolution:
1.50Å     R-factor:   0.196     R-free:   0.219
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
Date:
29-Aug-07     Release date:   22-Jan-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
291 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cyclin-dependent protein kinase holoenzyme complex   15 terms 
  Biological process     regulation of gene silencing   27 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
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.
 
  ABSTRACT  
 
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.  
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.