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: PDE4DDPDE3
EC: 3.1.4.17
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 Binding MOAD:  3SL4 IC50: 27 (nM) from 1 assay(s)
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 


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