4EDZ

Crystal structure of hH-PGDS with water displacing inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Investigation of the binding pocket of human hematopoietic prostaglandin (PG) D2 synthase (hH-PGDS): a tale of two waters.

Trujillo, J.I.Kiefer, J.R.Huang, W.Day, J.E.Moon, J.Jerome, G.M.Bono, C.P.Kornmeier, C.M.Williams, M.L.Kuhn, C.Rennie, G.R.Wynn, T.A.Carron, C.P.Thorarensen, A.

(2012) Bioorg Med Chem Lett 22: 3795-3799

  • DOI: https://doi.org/10.1016/j.bmcl.2012.04.004
  • Primary Citation of Related Structures:  
    4EC0, 4EDY, 4EDZ, 4EE0

  • PubMed Abstract: 

    The inhibition of hH-PGDS has been proposed as a potential target for the development of anti-allergic and anti-inflammatory drugs. Herein we describe our investigation of the binding pocket of this important enzyme and our observation that two water molecules bind to our inhibitors and the enzyme. A series of compounds were prepared to the probe the importance of the water molecules in determining the binding affinity of the inhibitors to the enzyme. The study provides insight into the binding requirements for the design of potent hH-PGDS inhibitors.


  • Organizational Affiliation

    Departments of Medicinal Chemistry, Pfizer Global Research and Development, Chesterfield, MO 63017, United States. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hematopoietic prostaglandin D synthase
A, B, C, D
199Homo sapiensMutation(s): 0 
Gene Names: GSTSHPGDSPGDSPTGDS2
EC: 5.3.99.2 (PDB Primary Data), 2.5.1.18 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for O60760 (Homo sapiens)
Explore O60760 
Go to UniProtKB:  O60760
PHAROS:  O60760
GTEx:  ENSG00000163106 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60760
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0O5
Query on 0O5

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
L [auth C],
N [auth D]
4-(3-methylisoquinolin-1-yl)-N-[2-(morpholin-4-yl)ethyl]benzamide
C23 H25 N3 O2
TUUADNJAZQZKLA-UHFFFAOYSA-N
GSH
Query on GSH

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
K [auth C],
M [auth D]
GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
G [auth B],
J [auth C]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0O5 BindingDB:  4EDZ IC50: 8.26 (nM) from 1 assay(s)
PDBBind:  4EDZ IC50: 8.26 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 
  • Space Group: I 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.468α = 90
b = 124.468β = 90
c = 105.927γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-16
    Type: Initial release
  • Version 1.1: 2013-01-02
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations