PDBsum entry 3frg

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Hydrolase/hydrolase inhibitor PDB id
Protein chain
335 a.a. *
ARS ×3
GOL ×2
Waters ×325
* Residue conservation analysis
PDB id:
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.
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
08-Jan-09     Release date:   12-Jan-10    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q07343  (PDE4B_HUMAN) -  cAMP-specific 3',5'-cyclic phosphodiesterase 4B
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',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.
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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