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PDBsum entry 3frg

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
3frg
Jmol
Contents
Protein chain
335 a.a. *
Ligands
SK4
ARS ×3
GOL ×2
Metals
_ZN
_MG
Waters ×325
* Residue conservation analysis
PDB id:
3frg
Name: Hydrolase/hydrolase inhibitor
Title: Catalytic domain of human phosphodiesterase 4b2b in complex with a quinoline inhibitor
Structure: Camp-specific 3',5'-cyclic phosphodiesterase 4b. Chain: a. Fragment: catalytic domain. Synonym: dpde4, pde32. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: dpde4, pde4b. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
1.70Å     R-factor:   0.210     R-free:   0.242
Authors: D.O.Somers,M.Neu
Key ref: C.J.Lunniss et al. (2009). Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration. Bioorg Med Chem Lett, 19, 1380-1385. PubMed id: 19195882 DOI: 10.1016/j.bmcl.2009.01.045
Date:
08-Jan-09     Release date:   12-Jan-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07343  (PDE4B_HUMAN) -  cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Seq:
Struc:
 
Seq:
Struc:
736 a.a.
335 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.1.4.53  - 3',5'-cyclic-AMP phosphodiesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate
Adenosine 3',5'-cyclic phosphate
Bound ligand (Het Group name = GOL)
matches with 46.00% similarity
+ H(2)O
= adenosine 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   1 term 
  Biochemical function     phosphoric diester hydrolase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmcl.2009.01.045 Bioorg Med Chem Lett 19:1380-1385 (2009)
PubMed id: 19195882  
 
 
Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration.
C.J.Lunniss, A.W.Cooper, C.D.Eldred, M.Kranz, M.Lindvall, F.S.Lucas, M.Neu, A.G.Preston, L.E.Ranshaw, A.J.Redgrave, J.Ed Robinson, T.J.Shipley, Y.E.Solanke, D.O.Somers, J.O.Wiseman.
 
  ABSTRACT  
 
Crystallography-driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of a series of quinoline derivatives that were highly potent and selective inhibitors of PDE4 with a good pharmacokinetic profile in the rat. Quinolines 43 and 48 have potential as oral medicines for the treatment of COPD.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21522681 M.Gutierrez, G.Vallejos, C.Fernández, A.Cárdenas, and I.Brito (2010).
1-[2-(4-Nitro-phen-yl)-5-(5-phenyl-1,2-oxazol-3-yl)-1,2,3,4-tetra-hydro-quinolin-4-yl]pyrrolidin-2-one monohydrate.
  Acta Crystallogr Sect E Struct Rep Online, 67, o175-o176.  
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