6ZTC

CRYSTAL STRUCTURE OF PROSTAGLANDIN D2 SYNTHASE IN COMPLEX WITH FRAGMENT 1A AT 1.84A RESOLUTION.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.167 

Starting Model: other
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.

Schulte, C.A.Deaton, D.N.Diaz, E.Do, Y.Gampe, R.T.Guss, J.H.Hancock, A.P.Hobbs, H.Hodgson, S.T.Holt, J.Jeune, M.R.Kahler, K.M.Kramer, H.F.Le, J.Mortenson, P.N.Musetti, C.Nolte, R.T.Orband-Miller, L.A.Peckham, G.E.Petrov, K.G.Pietrak, B.L.Poole, C.Price, D.J.Saxty, G.Shillings, A.Smalley Jr., T.L.Somers, D.O.Stewart, E.L.Stuart, J.D.Thomson, S.A.

(2021) Bioorg Med Chem Lett 47: 128113-128113

  • DOI: https://doi.org/10.1016/j.bmcl.2021.128113
  • Primary Citation of Related Structures:  
    6ZTC, 7JR6, 7JR8

  • PubMed Abstract: 

    Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.


  • Organizational Affiliation

    GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States. 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
200Homo sapiensMutation(s): 0 
Gene Names: HPGDSGSTSPGDSPTGDS2
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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GSH
Query on GSH

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
QPN (Subject of Investigation/LOI)
Query on QPN

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
1-[1-(3-fluorophenyl)-6,7-dihydro-4~{H}-pyrazolo[4,3-c]pyridin-5-yl]propan-1-one
C15 H16 F N3 O
PBPQRCMCEYVHIP-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
J [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
D [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
QPN BindingDB:  6ZTC IC50: 2800 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.167 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.071α = 90
b = 68.163β = 96.7
c = 68.517γ = 90
Software Package:
Software NamePurpose
MOSFLMdata processing
SCALAdata scaling
TRUNCATEdata reduction
REFMACphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2021-07-28 
  • Deposition Author(s): Somers, D.O.

Revision History  (Full details and data files)

  • Version 1.0: 2021-07-28
    Type: Initial release
  • Version 1.1: 2023-03-29
    Changes: Database references
  • Version 1.2: 2024-05-01
    Changes: Data collection, Refinement description