PDBsum entry 2o8h

Hydrolase

PDB id

2o8h

Loading ...

Contents

			Protein chain

					307 a.a. *

			Ligands

					227

			Metals

					_ZN


					_MG

			Waters ×312

* Residue conservation analysis

PDB id:

2o8h

Links

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

	Headers

	References

Protein chain

Q9QYJ6 (PDE10_RAT) - cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A from Rattus norvegicus

Seq: Struc:

Seq: Struc:					794 a.a. 307 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.3.1.4.17 - 3',5'-cyclic-nucleotide phosphodiesterase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H⁺

nucleoside 3',5'-cyclic phosphate	+	H2O	=	nucleoside 5'-phosphate	+	H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added 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.