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PDBsum entry 3bwj

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Transferase/transferase inhibitor PDB id
3bwj
Jmol
Contents
Protein chain
341 a.a. *
Ligands
ARX ×2
Waters ×175
* Residue conservation analysis
PDB id:
3bwj
Name: Transferase/transferase inhibitor
Title: Complex of pka with the bisubstrate protein kinase inhibitor compound arc-1034
Structure: Camp-dependent protein kinase, alpha-catalytic su chain: a. Synonym: pka c-alpha. Engineered: yes
Source: Bos taurus. Bovine. Organism_taxid: 9913. Gene: prkaca. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.201     R-free:   0.249
Authors: D.Lavogina,N.Koenig,A.Uri,D.Bossemeyer
Key ref: D.Lavogina et al. (2009). Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. J Med Chem, 52, 308-321. PubMed id: 19143565 DOI: 10.1021/jm800797n
Date:
09-Jan-08     Release date:   03-Feb-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00517  (KAPCA_BOVIN) -  cAMP-dependent protein kinase catalytic subunit alpha
Seq:
Struc:
351 a.a.
341 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.2.7.11.11  - cAMP-dependent protein 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     sperm midpiece   11 terms 
  Biological process     regulation of proteasomal protein catabolic process   18 terms 
  Biochemical function     nucleotide binding     13 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm800797n J Med Chem 52:308-321 (2009)
PubMed id: 19143565  
 
 
Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases.
D.Lavogina, M.Lust, I.Viil, N.König, G.Raidaru, J.Rogozina, E.Enkvist, A.Uri, D.Bossemeyer.
 
  ABSTRACT  
 
The crystal structure of a complex of the catalytic subunit (type alpha) of cAMP-dependent protein kinase (PKA C alpha) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosine-oligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4'-dehydroxymethyl-4'-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKBgamma.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20406699 D.Lavogina, C.K.Nickl, E.Enkvist, G.Raidaru, M.Lust, A.Vaasa, A.Uri, and W.R.Dostmann (2010).
Adenosine analogue-oligo-arginine conjugates (ARCs) serve as high-affinity inhibitors and fluorescence probes of type I cGMP-dependent protein kinase (PKGIalpha).
  Biochim Biophys Acta, 1804, 1857-1868.  
19774589 D.Lavogina, E.Enkvist, and A.Uri (2010).
Bisubstrate inhibitors of protein kinases: from principle to practical applications.
  ChemMedChem, 5, 23-34.  
19731277 R.Tiwari, and K.Parang (2009).
Protein conjugates of SH3-domain ligands and ATP-competitive inhibitors as bivalent inhibitors of protein kinases.
  Chembiochem, 10, 2445-2448.  
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