3SL3

Crystal structure of the apo form of the catalytic domain of PDE4D2

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history. 


Literature

Thiophene inhibitors of PDE4: Crystal structures show a second binding mode at the catalytic domain of PDE4D2.

Nankervis, J.L., Feil, S.C., Hancock, N.C., Zheng, Z., Ng, H.L., Morton, C.J., Holien, J.K., Ho, P.W., Frazzetto, M.M., Jennings, I.G., Manallack, D.T., Martin, T.J., Thompson, P.E., Parker, M.W.

(2011) Bioorg Med Chem Lett 21: 7089-7093

  • DOI: https://doi.org/10.1016/j.bmcl.2011.09.109
  • Primary Citation of Related Structures:  
    3SL3, 3SL4, 3SL5, 3SL6, 3SL8

  • PubMed Abstract: 

    PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.

    • Organizational Affiliation: 

    Medicinal Chemistry & Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville, Victoria, Australia.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
A, B, C, D
361Homo sapiensMutation(s): 0 
Gene Names: DPDE3, PDE4D
EC: 3.1.4.17 (PDB Primary Data), 3.1.4.53 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q08499 (Homo sapiens)
Explore Q08499 
Go to UniProtKB:  Q08499
PHAROS:  Q08499
GTEx:  ENSG00000113448 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ08499
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EPE
Query on EPE
Download Ideal Coordinates CCD File 
UA [auth C]4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
PEG
Query on PEG
Download Ideal Coordinates CCD File 
PA [auth B],
R [auth A],
RB [auth D],
TB [auth D]		DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
PO4
Query on PO4
Download Ideal Coordinates CCD File 
BC [auth D],
FB [auth C],
JA [auth B],
U [auth A]		PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
DMS
Query on DMS
Download Ideal Coordinates CCD File 
IB [auth D],
MA [auth B],
NA [auth B],
NB [auth D],
VA [auth C]		DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
AC [auth D]
DB [auth C]
EB [auth C]
HA [auth B]
IA [auth B]
AC [auth D],
DB [auth C],
EB [auth C],
HA [auth B],
IA [auth B],
S [auth A],
T [auth A],
ZB [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
AA [auth B]
AB [auth C]
BA [auth B]
BB [auth C]
CA [auth B]
AA [auth B],
AB [auth C],
BA [auth B],
BB [auth C],
CA [auth B],
CB [auth C],
CC [auth D],
DA [auth B],
DC [auth D],
E [auth A],
EA [auth B],
EC [auth D],
F [auth A],
FA [auth B],
FC [auth D],
G [auth A],
GA [auth B],
GB [auth C],
GC [auth D],
H [auth A],
HB [auth D],
HC [auth D],
I [auth A],
J [auth A],
JB [auth D],
K [auth A],
KA [auth B],
KB [auth D],
L [auth A],
LA [auth B],
LB [auth D],
M [auth A],
MB [auth D],
N [auth A],
O [auth A],
OA [auth B],
OB [auth D],
P [auth A],
PB [auth D],
Q [auth A],
QA [auth C],
QB [auth D],
RA [auth C],
SA [auth C],
SB [auth D],
TA [auth C],
UB [auth D],
V [auth A],
VB [auth D],
W [auth A],
WA [auth C],
WB [auth D],
X [auth A],
XA [auth C],
XB [auth D],
Y [auth A],
YA [auth C],
YB [auth D],
Z [auth B],
ZA [auth C]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.269α = 90
b = 111.757β = 90
c = 160.279γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2011-10-26 
    • Deposition Author(s): Feil, S.F.

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-26
    Type: Initial release
  • Version 1.1: 2011-12-14
    Changes: Database references
  • Version 1.2: 2017-11-08
    Changes: Advisory, Refinement description
  • Version 1.3: 2024-02-28
    Changes: Advisory, Data collection, Database references, Derived calculations