PDBsum entry 2pw3

Hydrolase

PDB id: 2pw3

Contents

Protein chains

327 a.a. *

Ligands

CMP ×2

Metals

_ZN ×2

Waters ×528

* Residue conservation analysis

PDB id:

2pw3

Name:

Hydrolase

Title:

Structure of the pde4d-camp complex

Structure:

Camp-specific 3',5'-cyclic phosphodiesterase 4d. Chain: a, b. Fragment: catalytic domain. Synonym: dpde3, pde43. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pde4d. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.56Å R-factor: 0.212 R-free: 0.231

Authors:

H.Wang,H.Robinson,H.Ke

Key ref:

H.Wang et al. (2007). The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10. J Mol Biol, 371, 302-307. PubMed id: 17582435 DOI: 10.1016/j.jmb.2007.05.060

Date:

10-May-07 Release date: 23-Oct-07

Protein chains

Q08499  (PDE4D_HUMAN) -  3',5'-cyclic-AMP phosphodiesterase 4D from Homo sapiens

Seq: 809 a.a.

Struc: 327 a.a.*

* 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.
• Reaction: 3',5'-cyclic AMP + H2O = AMP + H⁺

3',5'-cyclic AMP (Bound ligand (Het Group name = CMP) corresponds exactly) + H2O = AMP + H(+)

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

Added reference

DOI no: 10.1016/j.jmb.2007.05.060

J Mol Biol 371:302-307 (2007)

PubMed id: 17582435

The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10.

H.Wang, H.Robinson, H.Ke.

ABSTRACT

Phosphodiesterases (PDEs) are key enzymes that control the cellular concentrations of the second messengers cAMP and cGMP. The mechanism for selective recognition of substrates cAMP and cGMP by individual PDE families remains a puzzle. To understand the mechanism for substrate recognition by PDE enzymes, the crystal structure of the catalytic domain of an inactive D201N mutant of PDE4D2 in complex with substrate cAMP has been determined at 1.56 A resolution. The structure shows that Gln369 forms only one hydrogen bond with the adenine of cAMP. This finding provides experimental evidence against the hypothesis of two hydrogen bonds between the invariant glutamine and the substrate cAMP in PDE4, and thus suggests that the widely circulated "glutamine switch" model is unlikely the mechanism for substrate recognition by PDEs. A structure comparison between PDE4D2-cAMP and PDE10A2-cAMP reveals an anti configuration of cAMP in PDE4D2 but syn in PDE10A2, in addition to different contact patterns of cAMP in these two structures. These observations imply that individual PDE families have their characteristic mechanisms for substrate recognition.

Selected figure(s)

Figure 1.
Figure 1. Structure of the PDE4D D201N catalytic domain. (a) Ribbons diagram. The large red ball represents a zinc ion. The green sticks are the residues at the active site of the PDE4D2 D201N mutant. (b) Superposition of the active site residues of the wild-type PDE4D2 (blue sticks) over those of the D201N mutant. The zinc ion has the same position in the wild-type and D201N structures. The magnesium ion is from the wild-type PDE4D2.

Figure 3.
Figure 3. Structural superposition of PDE4D2–cAMP (green bonds and labels) over PDE10A2–cAMP (blue bonds and labels, and gold for cAMP). The bound cAMP has the anti configuration in PDE4D2 and syn in PDE10A2.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2007, 371, 302-307) copyright 2007.

Figures were selected by the author.