3SL4

Crystal structure of the catalytic domain of PDE4D2 with compound 10D

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


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: PDE4D, DPDE3
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 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
JN4
Query on JN4
Download Ideal Coordinates CCD File 
HB [auth C],
HC [auth D],
RA [auth B],
X [auth A]		ethenyl 6-(ethenylcarbamoyl)-2-[(phenylacetyl)amino]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate
C21 H21 N3 O4 S
WQVFFOUZABKGIL-UHFFFAOYSA-N
EPE
Query on EPE
Download Ideal Coordinates CCD File 
EA [auth B],
YA [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 
BC [auth D],
JB [auth D],
N [auth A],
UB [auth D],
YB [auth D]		DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
PO4
Query on PO4
Download Ideal Coordinates CCD File 
GB [auth C],
GC [auth D],
QA [auth B],
V [auth A]		PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
DMS
Query on DMS
Download Ideal Coordinates CCD File 
AB [auth C]
FA [auth B]
FC [auth D]
I [auth A]
QB [auth D]
AB [auth C],
FA [auth B],
FC [auth D],
I [auth A],
QB [auth D],
RB [auth D],
VB [auth D],
Z [auth A]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
BA [auth B]
CA [auth B]
E [auth A]
F [auth A]
KB [auth D]
BA [auth B],
CA [auth B],
E [auth A],
F [auth A],
KB [auth D],
LB [auth D],
TA [auth C],
UA [auth C]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
AA [auth A]
AC [auth D]
BB [auth C]
CB [auth C]
CC [auth D]
AA [auth A],
AC [auth D],
BB [auth C],
CB [auth C],
CC [auth D],
DA [auth B],
DB [auth C],
DC [auth D],
EB [auth C],
EC [auth D],
FB [auth C],
G [auth A],
GA [auth B],
H [auth A],
HA [auth B],
IA [auth B],
IB [auth D],
J [auth A],
JA [auth B],
K [auth A],
KA [auth B],
L [auth A],
LA [auth B],
M [auth A],
MA [auth B],
MB [auth D],
NA [auth B],
NB [auth D],
O [auth A],
OA [auth B],
OB [auth D],
P [auth A],
PA [auth B],
PB [auth D],
Q [auth A],
R [auth A],
S [auth A],
SA [auth C],
SB [auth D],
T [auth A],
TB [auth D],
U [auth A],
VA [auth C],
W [auth A],
WA [auth C],
WB [auth D],
XA [auth C],
XB [auth D],
Y [auth A],
ZA [auth C],
ZB [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
JN4 PDBBind:  3SL4 IC50: 27 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.375α = 90
b = 111.088β = 90
c = 161.215γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


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: Refinement description
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations