1V40

First Inhibitor Complex Structure of Human Hematopoietic Prostaglandin D Synthase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase.

Inoue, T.Okano, Y.Kado, Y.Aritake, K.Irikura, D.Uodome, N.Okazaki, N.Kinugasa, S.Shishitani, H.Matsumura, H.Kai, Y.Urade, Y.

(2004) J Biochem 135: 279-283

  • DOI: https://doi.org/10.1093/jb/mvh033
  • Primary Citation of Related Structures:  
    1V40

  • PubMed Abstract: 

    Hematopoietic prostaglandin (PG) D synthase (H-PGDS) is responsible for the production of PGD(2) as an allergy or inflammation mediator in mast and Th2 cells. We determined the X-ray structure of human H-PGDS complexed with an inhibitor, 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride (BSPT) at 1.9 A resolution in the presence of Mg(2+). The styryl group of the inhibitor penetrated to the bottom of the active site cleft, and the tetrazole ring was stabilized by the stacking interaction with Trp104, inducing large movement around the alpha5-helix, which caused the space group of the complex crystal to change from P2(1) to P1 upon binding of BSPT. The phthalhydrazidyl group of BSPT exhibited steric hindrance due to the cofactor, glutathione (GSH), increasing the IC(50) value of BSPT for human H-PGDS from 36.2 micro M to 98.1 micro M upon binding of Mg(2+), because the K(m) value of GSH for human H-PGDS was decreased from 0.60 micro M in the presence of EDTA to 0.14 micro M in the presence of Mg(2+). We have to avoid steric hindrance of the GSH molecule that was stabilized by intracellular Mg(2+) in the mM range in the cytosol for further development of structure-based anti-allergic drugs.


  • Organizational Affiliation

    Department of Materials Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutathione-requiring prostaglandin D synthase
A, B, C, D
198Homo sapiensMutation(s): 0 
EC: 5.3.99.2
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
O16
Query on O16

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B],
O [auth C],
S [auth D]
3-(1,3-BENZOTHIAZOL-2-YL)-2-(1,4-DIOXO-1,2,3,4-TETRAHYDROPHTHALAZIN-6-YL)-5-[(E)-2-PHENYLVINYL]-3H-TETRAAZOL-2-IUM
C24 H16 N7 O2 S
BEIGFKLRGRRJJA-JLHYYAGUSA-O
GSH
Query on GSH

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

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
M [auth B]
P [auth C]
Q [auth C]
H [auth A],
I [auth A],
M [auth B],
P [auth C],
Q [auth C],
T [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A],
J [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.288α = 93.25
b = 49.237β = 89.98
c = 94.526γ = 90.01
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-07
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description