5AIS

Complex of human hematopoietic prostagandin D2 synthase (hH-PGDS) in complex with an active site inhibitor.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.233 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Identification of Indole Inhibitors of Human Hematopoietic Prostaglandin D2 Synthase (Hh-Pgds).

Edfeldt, F.Even, J.Lepisto, M.Ward, A.Petersen, J.Wissler, L.Rohman, M.Sivars, U.Svensson, K.Perry, M.Feierberg, I.Zhou, X.H.Hansson, T.Narjes, F.

(2015) Bioorg Med Chem Lett 25: 2496

  • DOI: https://doi.org/10.1016/j.bmcl.2015.04.065
  • Primary Citation of Related Structures:  
    5AIS, 5AIV, 5AIX

  • PubMed Abstract: 

    Human H-PGDS has shown promise as a potential target for anti-allergic and anti-inflammatory drugs. Here we describe the discovery of a novel class of indole inhibitors, identified through focused screening of 42,000 compounds and evaluated using a series of hit validation assays that included fluorescence polarization binding, 1D NMR, ITC and chromogenic enzymatic assays. Compounds with low nanomolar potency, favorable physico-chemical properties and inhibitory activity in human mast cells have been identified. In addition, our studies suggest that the active site of hH-PGDS can accommodate larger structural diversity than previously thought, such as the introduction of polar groups in the inner part of the binding pocket.


  • Organizational Affiliation

    Discovery Sciences, Innovative Medicines, AstraZeneca R&D, 431 83 Molndal, Sweden. Electronic address: [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 
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
CWC
Query on CWC

Download Ideal Coordinates CCD File 
E [auth A],
G [auth B],
J [auth C],
L [auth D]
4-(dimethylamino)-N-[5-(1H-indol-4-yl)pyridin-3-yl]butanamide
C19 H22 N4 O
QVBOWRMZONBBIK-UHFFFAOYSA-N
GSH
Query on GSH

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

Download Ideal Coordinates CCD File 
H [auth B],
M [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CWC BindingDB:  5AIS Kd: 570 (nM) from 1 assay(s)
IC50: min: 180, max: 820 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.233 
  • Space Group: I 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.802α = 90
b = 124.802β = 90
c = 106.884γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-03
    Type: Initial release
  • Version 1.1: 2015-06-10
    Changes: Database references
  • Version 1.2: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other