3SL5

Crystal structure of the catalytic domain of PDE4D2 complexed with compound 10d

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.175 

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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
359Homo sapiensMutation(s): 0 
Gene Names: DPDE3, PDE4D
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 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
J25
Query on J25
Download Ideal Coordinates CCD File 
CA [auth D],
G [auth A],
M [auth B],
S [auth C]		diethyl 2-[(thiophen-2-ylacetyl)amino]-4,7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylate
C19 H22 N2 O5 S2
ZDMGIZFQKKDWAO-UHFFFAOYSA-N
EPE
Query on EPE
Download Ideal Coordinates CCD File 
P [auth C]4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
DMS
Query on DMS
Download Ideal Coordinates CCD File 
I [auth A]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
AA [auth D]
BA [auth D]
E [auth A]
F [auth A]
K [auth B]
AA [auth D],
BA [auth D],
E [auth A],
F [auth A],
K [auth B],
L [auth B],
Q [auth C],
R [auth C]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
DA [auth D]
EA [auth D]
FA [auth D]
GA [auth D]
H [auth A]
DA [auth D],
EA [auth D],
FA [auth D],
GA [auth D],
H [auth A],
HA [auth D],
IA [auth D],
J [auth A],
N [auth B],
O [auth B],
T [auth C],
U [auth C],
V [auth C],
W [auth C],
X [auth C],
Y [auth D],
Z [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
J25 PDBBind:  3SL5 IC50: 22 (nM) from 1 assay(s)
BindingDB:  3SL5 IC50: 22 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.394α = 90
b = 109.966β = 90
c = 159.613γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


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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