PDBsum entry 2wey

Hydrolase

PDB id: 2wey

Contents

Protein chain

324 a.a. *

Ligands

EV1 ×2

Metals

_MG ×2

_ZN ×2

Waters ×23

* Residue conservation analysis

PDB id:

2wey

Name:

Hydrolase

Title:

Human pde-papaverine complex obtained by ligand soaking of cross- linked protein crystals

Structure:

Camp and camp-inhibited cgmp 3', 5'-cyclic phosphodiesterase. Chain: a, b. Fragment: catalytic domain, residues 467-807. Synonym: phosphodiesterase 10a2, pde10a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.80Å R-factor: 0.242 R-free: 0.300

Authors:

O.A.Andersen,D.L.Schonfeld,I.Toogood-Johnson,B.Felicetti,C.Albrecht, T.Fryatt,M.Whittaker,D.Hallett,J.Barker

Key ref:

O.A.Andersen et al. (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. PubMed id: 19622871 DOI: 10.1107/S0907444909017855

Date:

02-Apr-09 Release date: 28-Jul-09

Protein chains

Q9Y233  (PDE10_HUMAN) -  cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A from Homo sapiens

Seq: 1055 a.a.

Struc: 324 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.4.17 - 3',5'-cyclic-nucleotide phosphodiesterase.
• Reaction: a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H⁺

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

Added reference

DOI no: 10.1107/S0907444909017855

Acta Crystallogr D Biol Crystallogr 65:872-874 (2009)

PubMed id: 19622871

Cross-linking of protein crystals as an aid in the generation of binary protein-ligand crystal complexes, exemplified by the human PDE10a-papaverine structure.

O.A.Andersen, D.L.Schönfeld, I.Toogood-Johnson, B.Felicetti, C.Albrecht, T.Fryatt, M.Whittaker, D.Hallett, J.Barker.

ABSTRACT

Protein crystallography has proven to be an effective method of obtaining high-resolution structures of protein-ligand complexes. However, in certain cases only apoprotein structures are readily available and the generation of crystal complexes is more problematic. Some crystallographic systems are not amenable to soaking of ligands owing to crystal-packing effects and many protein-ligand complexes do not crystallize under the same conditions as used for the apoprotein. Using crystals of human phosphodiesterase 10a (hPDE10a) as an example of such a challenging crystallographic system, the structure of the complex with papaverine was obtained to 2.8 A resolution using protein crystals cross-linked by glutaraldehyde prior to soaking of the ligand. Inspection of the electron-density maps suggested that the correct mode of binding was obtained in one of the two monomers in the asymmetric unit and inspection of crystal-packing contacts explained why cocrystallization experiments and soaking of crystals that were not cross-linked were unsuccessful.

Selected figure(s)

Figure 1.
Figure 1 Stereo figure of the active site of monomer B in the hPDE10a-papaverine crystal structure. F[o] - F[c] electron density is contoured at 2.0 . Hydrogen-bonding interactions are shown as dotted lines to Gln726. The protein and papaverine are shown as a stick models with green and magenta C atoms, respectively. Zinc and magnesium are shown as purple and red spheres, respectively.

The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2009, 65, 872-874) copyright 2009.

Figure was selected by an automated process.