1Q9M

Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.224 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity

Huai, Q.Wang, H.Sun, Y.Kim, H.Y.Liu, Y.Ke, H.

(2003) Structure 11: 865-873

  • DOI: https://doi.org/10.1016/s0969-2126(03)00123-0
  • Primary Citation of Related Structures:  
    1OYN, 1Q9M

  • PubMed Abstract: 

    Selective inhibitors against the 11 families of cyclic nucleotide phosphodiesterases (PDEs) are used to treat various human diseases. How the inhibitors selectively bind the conserved PDE catalytic domains is unknown. The crystal structures of the PDE4D2 catalytic domain in complex with (R)- or (R,S)-rolipram suggest that inhibitor selectivity is determined by the chemical nature of amino acids and subtle conformational changes of the binding pockets. The conformational states of Gln369 in PDE4D2 may play a key role in inhibitor recognition. The corresponding Y329S mutation in PDE7 may lead to loss of the hydrogen bonds between rolipram and Gln369 and is thus a possible reason explaining PDE7's insensitivity to rolipram inhibition. Docking of the PDE5 inhibitor sildenafil into the PDE4 catalytic pocket further helps understand inhibitor selectivity.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cAMP-specific phosphodiesterase PDE4D2
A, B, C, D
360Homo sapiensMutation(s): 0 
Gene Names: 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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ROL
Query on ROL

Download Ideal Coordinates CCD File 
G [auth A],
J [auth B],
M [auth C],
P [auth D]
ROLIPRAM
C16 H21 N O3
HJORMJIFDVBMOB-LBPRGKRZSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
H [auth B]
I [auth B]
K [auth C]
E [auth A],
F [auth A],
H [auth B],
I [auth B],
K [auth C],
L [auth C],
N [auth D],
O [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ROL PDBBind:  1Q9M IC50: 330 (nM) from 1 assay(s)
Binding MOAD:  1Q9M IC50: 330 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.224 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.272α = 90
b = 112.493β = 90
c = 160.908γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-09-02
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations