PDBsum entry 2fm0

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
334 a.a. *
M98 ×4
_ZN ×4
_MG ×4
Waters ×374
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of pde4d in complex with l-869298
Structure: Camp-specific 3',5'-cyclic phosphodiesterase 4d. Chain: a, b, c, d. Fragment: catalytic domain. Synonym: dpde3, pde43. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pde4d2. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.223     R-free:   0.245
Authors: Q.Huai,Y.Sun,H.Wang,D.Macdonald,R.Aspiotis,H.Robinson, Z.Huang,H.Ke
Key ref: Q.Huai et al. (2006). Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase. J Med Chem, 49, 1867-1873. PubMed id: 16539372 DOI: 10.1021/jm051273d
06-Jan-06     Release date:   28-Mar-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q08499  (PDE4D_HUMAN) -  cAMP-specific 3',5'-cyclic phosphodiesterase 4D
809 a.a.
334 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 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
+ 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     catalytic activity     3 terms  


    Added reference    
DOI no: 10.1021/jm051273d J Med Chem 49:1867-1873 (2006)
PubMed id: 16539372  
Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase.
Q.Huai, Y.Sun, H.Wang, D.Macdonald, R.Aspiotis, H.Robinson, Z.Huang, H.Ke.
Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to preserve the pivotal interactions between the Mg-bound waters and the N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanations for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20196770 X.Li, S.Vadrevu, A.Dunlop, J.Day, N.Advant, J.Troeger, E.Klussmann, E.Jaffrey, R.T.Hay, D.R.Adams, M.D.Houslay, and G.S.Baillie (2010).
Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK.
  Biochem J, 428, 55-65.  
18983167 H.Wang, Z.Yan, S.Yang, J.Cai, H.Robinson, and H.Ke (2008).
Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity.
  Biochemistry, 47, 12760-12768.
PDB codes: 3ecm 3ecn
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