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PDBsum entry 2o8h

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protein ligands metals links
Hydrolase PDB id
2o8h
Jmol
Contents
Protein chain
307 a.a. *
Ligands
227
Metals
_ZN
_MG
Waters ×312
* Residue conservation analysis
PDB id:
2o8h
Name: Hydrolase
Title: Crystal structure of the catalytic domain of rat phosphodiesterase 10a
Structure: Phosphodiesterase-10a. Chain: a. Fragment: catalytic domain. Synonym: pde10a2. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: pde10a, pde10a. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
Resolution:
1.80Å     R-factor:   0.227     R-free:   0.273
Authors: J.Pandit,E.S.Marr
Key ref: T.A.Chappie et al. (2007). Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors. J Med Chem, 50, 182-185. PubMed id: 17228859 DOI: 10.1021/jm060653b
Date:
12-Dec-06     Release date:   09-Jan-07    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9QYJ6  (PDE10_RAT) -  cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Seq:
Struc:
 
Seq:
Struc:
794 a.a.
307 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.3.1.4.17  - 3',5'-cyclic-nucleotide phosphodiesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
Nucleoside 3',5'-cyclic phosphate
+ H(2)O
= nucleoside 5'-phosphate
   Enzyme class 2: E.C.3.1.4.35  - 3',5'-cyclic-GMP phosphodiesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate
Guanosine 3',5'-cyclic phosphate
+ H(2)O
= guanosine 5'-phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
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  

 

 
    reference    
 
 
DOI no: 10.1021/jm060653b J Med Chem 50:182-185 (2007)
PubMed id: 17228859  
 
 
Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors.
T.A.Chappie, J.M.Humphrey, M.P.Allen, K.G.Estep, C.B.Fox, L.A.Lebel, S.Liras, E.S.Marr, F.S.Menniti, J.Pandit, C.J.Schmidt, M.Tu, R.D.Williams, F.V.Yang.
 
  ABSTRACT  
 
A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20062862 C.Duplais, A.Krasovskiy, A.Wattenberg, and B.H.Lipshutz (2010).
Cross-couplings between benzylic and aryl halides "on water": synthesis of diarylmethanes.
  Chem Commun (Camb), 46, 562-564.  
19622871 O.A.Andersen, D.L.Schönfeld, I.Toogood-Johnson, B.Felicetti, C.Albrecht, T.Fryatt, M.Whittaker, D.Hallett, and J.Barker (2009).
Cross-linking of protein crystals as an aid in the generation of binary protein-ligand crystal complexes, exemplified by the human PDE10a-papaverine structure.
  Acta Crystallogr D Biol Crystallogr, 65, 872-874.
PDB code: 2wey
18998737 J.A.Siuciak (2008).
The role of phosphodiesterases in schizophrenia : therapeutic implications.
  CNS Drugs, 22, 983-993.  
18931772 M.Amatore, and C.Gosmini (2008).
Synthesis of functionalised diarylmethanes via a cobalt-catalysed cross-coupling of arylzinc species with benzyl chlorides.
  Chem Commun (Camb), (), 5019-5021.  
18614542 S.E.Martinez, C.C.Heikaus, R.E.Klevit, and J.A.Beavo (2008).
The structure of the GAF A domain from phosphodiesterase 6C reveals determinants of cGMP binding, a conserved binding surface, and a large cGMP-dependent conformational change.
  J Biol Chem, 283, 25913-25919.
PDB code: 3dba
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.