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PDBsum entry 3hmv

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
3hmv
Jmol
Contents
Protein chains
351 a.a. *
Ligands
HBT ×2
GOL
Metals
_ZN ×2
_MG ×2
Waters ×255
* Residue conservation analysis
PDB id:
3hmv
Name: Hydrolase
Title: Catalytic domain of human phosphodiesterase 4b2b in complex tetrahydrobenzothiophene inhibitor
Structure: Camp-specific 3',5'-cyclic phosphodiesterase 4b. Chain: a, b. Fragment: catalytic domain, unp residues 324-700. Synonym: dpde4, pde32. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pde4b, dpde4. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.23Å     R-factor:   0.176     R-free:   0.226
Authors: D.O.Somers,M.Neu
Key ref: M.Kranz et al. (2009). Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode. Bioorg Med Chem, 17, 5336-5341. PubMed id: 19525117 DOI: 10.1016/j.bmc.2009.03.061
Date:
29-May-09     Release date:   09-Jun-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q07343  (PDE4B_HUMAN) -  cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Seq:
Struc:
 
Seq:
Struc:
736 a.a.
351 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     catalytic activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmc.2009.03.061 Bioorg Med Chem 17:5336-5341 (2009)
PubMed id: 19525117  
 
 
Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode.
M.Kranz, M.Wall, B.Evans, A.Miah, S.Ballantine, C.Delves, B.Dombroski, J.Gross, J.Schneck, J.P.Villa, M.Neu, D.O.Somers.
 
  ABSTRACT  
 
A PDE4B over 4D-selective inhibitor programme was initiated to capitalise on the recently discovered predominance of the PDE4B subtype in inflammatory cell regulation. The SAR of a tetrahydrobenzothiophene (THBT) series did not agree with either of two proposed docking modes in the 4B binding site. A subsequent X-ray co-crystal structure determination revealed that the THBT ligand displaces the Gln-443 residue, invariably ligand-anchoring in previous PDE4 co-crystal structures, and even shifts helix-15 by 1-2A. For the first time, several residues of the C-terminus previously proposed to be involved in subtype selectivity are resolved and three of them extend into the ligand binding site potentially allowing for selective drug design.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20191319 Y.Huang, and A.Dömling (2011).
The Gewald multicomponent reaction.
  Mol Divers, 15, 3.  
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