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PDBsum entry 4jin

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protein ligands links
Transferase/transferase inhibitor PDB id
4jin
Jmol
Contents
Protein chain
254 a.a.
Ligands
1L7
Waters ×87
PDB id:
4jin
Name: Transferase/transferase inhibitor
Title: X-ray crystal structure of archaeoglobus fulgidus rio1 bound n-benzyl-2-cyano-3-(pyridine-4-yl)acrylamide (wp1086)
Structure: Rio-type serine/threonine-protein kinase rio1. Chain: a. Synonym: afrio1. Engineered: yes
Source: Archaeoglobus fulgidus. Organism_taxid: 224325. Strain: atcc 49558 / vc-16 / dsm 4304 / jcm 9628 / nbrc 100 gene: af_1804, rio1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.182     R-free:   0.241
Authors: M.Mielecki,K.Krawiec,I.Kiburu,K.Grzelak,Z.Wlodzimierz,B.Kier K.Kowa,I.Fokt,S.Szymanski,S.Piotr,W.Szeja,W.Priebe,B.Lesyng N.Laronde-Leblanc
Key ref: M.Mielecki et al. (2013). Development of novel molecular probes of the Rio1 atypical protein kinase. Biochim Biophys Acta, 1834, 1292-1301. PubMed id: 23523885 DOI: 10.1016/j.bbapap.2013.03.012
Date:
06-Mar-13     Release date:   24-Apr-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O28471  (RIO1_ARCFU) -  RIO-type serine/threonine-protein kinase Rio1
Seq:
Struc:
258 a.a.
254 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.1  - Non-specific serine/threonine 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!
  Biological process     phosphorylation   2 terms 
  Biochemical function     catalytic activity     9 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bbapap.2013.03.012 Biochim Biophys Acta 1834:1292-1301 (2013)
PubMed id: 23523885  
 
 
Development of novel molecular probes of the Rio1 atypical protein kinase.
M.Mielecki, K.Krawiec, I.Kiburu, K.Grzelak, W.Zagórski, B.Kierdaszuk, K.Kowa, I.Fokt, S.Szymanski, P.Swierk, W.Szeja, W.Priebe, B.Lesyng, N.LaRonde-LeBlanc.
 
  ABSTRACT  
 
The RIO kinases are essential protein factors required for the synthesis of new ribosomes in eukaryotes. Conserved in archaeal organisms as well, RIO kinases are among the most ancient of protein kinases. Their exact molecular mechanisms are under investigation and progress of this research would be significantly improved with the availability of suitable molecular probes that selectively block RIO kinases. RIO kinases contain a canonical eukaryotic protein kinase fold, but also display several unusual structural features that potentially create opportunity for the design of selective inhibitors. In an attempt to identify structural leads to target the RIO kinases, a series of pyridine caffeic acid benzyl amides (CABA) were tested for their ability to inhibit the autophosphorylation activity of Archeaoglobus fulgidus Rio1 (AfRio1). Screening of a small library of CABA molecules resulted in the identification of four compounds that measurably inhibited AfRio1 activity. Additional biochemical characterization of binding and inhibition activity of these compounds demonstrated an ATP competitive inhibition mode, and allowed identification of the functional groups that result in the highest binding affinity. In addition, docking of the compound to the structure of Rio1 and determination of the X-ray crystal structure of a model compound (WP1086) containing the desired functional groups allowed detailed analysis of the interactions between these compounds and the enzyme. Furthermore, the X-ray crystal structure demonstrated that these compounds stabilize an inactive form of the enzyme. Taken together, these results provide an important step in identification of a scaffold for the design of selective molecular probes to study molecular mechanisms of Rio1 kinases in vitro and in vivo. In addition, it provides a rationale for the future design of potent inhibitors with drug-like properties targeting an inactive form of the enzyme. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).