 |
PDBsum entry 2fm0
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
Crystal structure of pde4d in complex with l-869298
|
|
Structure:
|
|
Camp-specific 3',5'-cyclic phosphodiesterase 4d. Chain: a, b, c, d. Fragment: catalytic domain. Synonym: dpde3, pde43. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: pde4d2. Expressed in: escherichia coli. Expression_system_taxid: 562.
|
|
Resolution:
|
|
|
2.00Å
|
R-factor:
|
0.223
|
R-free:
|
0.245
|
|
|
Authors:
|
|
Q.Huai,Y.Sun,H.Wang,D.Macdonald,R.Aspiotis,H.Robinson,Z.Huang,H.Ke
|
|
Key ref:
|
|
Q.Huai
et al.
(2006).
Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase.
J Med Chem,
49,
1867-1873.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
06-Jan-06
|
Release date:
|
28-Mar-06
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q08499
(PDE4D_HUMAN) -
3',5'-cyclic-AMP phosphodiesterase 4D from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
809 a.a.
334 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
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
|
+
|
H2O
|
=
|
AMP
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
J Med Chem
49:1867-1873
(2006)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase.
|
|
Q.Huai,
Y.Sun,
H.Wang,
D.Macdonald,
R.Aspiotis,
H.Robinson,
Z.Huang,
H.Ke.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a
number of disorders including asthma and chronic obstructive pulmonary disease.
Here we report the biochemical characterization on the second generation
inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and
their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold
affinity difference, both enantiomers interact with the same sets of residues in
the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to
preserve the pivotal interactions between the Mg-bound waters and the N-oxide of
pyridine. These structures support a model in which inhibitors are anchored by
the invariant glutamine at one end and the metal-pocket residues at another end.
This model provides explanations for most of the observed structure-activity
relationship and the metal ion dependency of the catechol-ether based inhibitors
and should facilitate their further design.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
X.Li,
S.Vadrevu,
A.Dunlop,
J.Day,
N.Advant,
J.Troeger,
E.Klussmann,
E.Jaffrey,
R.T.Hay,
D.R.Adams,
M.D.Houslay,
and
G.S.Baillie
(2010).
Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK.
|
| |
Biochem J,
428,
55-65.
|
|
|
|
|
|
|
H.Wang,
Z.Yan,
S.Yang,
J.Cai,
H.Robinson,
and
H.Ke
(2008).
Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity.
|
| |
Biochemistry,
47,
12760-12768.
|
|
|
PDB codes:
|
|
|
|
|
|
|
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
codes are
shown on the right.
|
|
Links
