1SOJ

CATALYTIC DOMAIN OF HUMAN PHOSPHODIESTERASE 3B IN COMPLEX WITH IBMX


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.235 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Crystal Structure of Human Phosphodiesterase 3B: Atomic Basis for Substrate and Inhibitor Specificity

Scapin, G.Patel, S.B.Chung, C.Varnerin, J.P.Edmondson, S.D.Mastracchio, A.Parmee, E.R.Singh, S.B.Becker, J.W.Van Der Ploeg, L.H.Tota, M.R.

(2004) Biochemistry 43: 6091-6100

  • DOI: https://doi.org/10.1021/bi049868i
  • Primary Citation of Related Structures:  
    1SO2, 1SOJ

  • PubMed Abstract: 

    Phosphodiesterases (PDEs) are enzymes that modulate cyclic nucleotide signaling and as such are clinical targets for a range of disorders including congestive heart failure, erectile dysfunction, and inflammation. The PDE3 family comprises two highly homologous subtypes expressed in different tissues, and inhibitors of this family have been shown to increase lipolysis in adipocytes. A specific PDE3B (the lipocyte-localized subtype) inhibitor would be a very useful tool to evaluate the effects of PDE3 inhibition on lipolysis and metabolic rate and might become a novel tool for treatment of obesity. We report here the three-dimensional structures of the catalytic domain of human PDE3B in complex with a generic PDE inhibitor and a novel PDE3 selective inhibitor. These structures explain the dual cAMP/cGMP binding capabilities of PDE3, provide the molecular basis for inhibitor specificity, and can supply a valid platform for the design of improved compounds.


  • Organizational Affiliation

    Departments of Medicinal Chemistry, Merck & Co., Rahway, New Jersey 07065, USA. giovanna_scapin@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cGMP-inhibited 3',5'-cyclic phosphodiesterase B
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L
420Homo sapiensMutation(s): 0 
Gene Names: PDE3B
EC: 3.1.4.17
UniProt & NIH Common Fund Data Resources
Find proteins for Q13370 (Homo sapiens)
Explore Q13370 
Go to UniProtKB:  Q13370
PHAROS:  Q13370
GTEx:  ENSG00000152270 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13370
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IBM
Query on IBM

Download Ideal Coordinates CCD File 
AA [auth E]
DA [auth F]
GA [auth G]
JA [auth H]
MA [auth I]
AA [auth E],
DA [auth F],
GA [auth G],
JA [auth H],
MA [auth I],
O [auth A],
PA [auth J],
R [auth B],
SA [auth K],
U [auth C],
VA [auth L],
X [auth D]
3-ISOBUTYL-1-METHYLXANTHINE
C10 H14 N4 O2
APIXJSLKIYYUKG-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
BA [auth F]
CA [auth F]
EA [auth G]
FA [auth G]
HA [auth H]
BA [auth F],
CA [auth F],
EA [auth G],
FA [auth G],
HA [auth H],
IA [auth H],
KA [auth I],
LA [auth I],
M [auth A],
N [auth A],
NA [auth J],
OA [auth J],
P [auth B],
Q [auth B],
QA [auth K],
RA [auth K],
S [auth C],
T [auth C],
TA [auth L],
UA [auth L],
V [auth D],
W [auth D],
Y [auth E],
Z [auth E]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IBM PDBBind:  1SOJ IC50: 242 (nM) from 1 assay(s)
BindingDB:  1SOJ IC50: 242 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.235 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 275.046α = 90
b = 147.078β = 109.84
c = 253.485γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
CNXrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-11
    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: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description