3VI5

Human hematopoietic prostaglandin D synthase inhibitor complex structures


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.179 

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Ligand Structure Quality Assessment 


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Literature

Human hematopoietic prostaglandin D synthase inhibitor complex structures

Kado, Y.Aritake, K.Uodome, N.Okano, Y.Okazaki, N.Matsumura, H.Urade, Y.Inoue, T.

(2012) J Biochem 151: 447-455

  • DOI: https://doi.org/10.1093/jb/mvs024
  • Primary Citation of Related Structures:  
    3VI5, 3VI7

  • PubMed Abstract: 

    In mast and Th2 cells, hematopoietic prostaglandin (PG) D synthase (H-PGDS) catalyses the isomerization of PGH(2) in the presence of glutathione (GSH) to produce the allergic and inflammatory mediator PGD(2). We determined the X-ray structures of human H-PGDS inhibitor complexes with 1-amino-4-{4-[4-chloro-6-(2-sulpho-phenylamino)-[1,3,5]triazin-2-ylmethyl]-3-sulpho-phenylamino}-9,10-dioxo-9,10-dihydro-anthracene-2-sulphonic acid (Cibacron Blue) and 1-amino-4-(4-aminosulphonyl) phenyl-anthraquinone-2-sulphonic acid (APAS) at 2.0 Å resolution. When complexed with H-PGDS, Cibacron Blue had an IC(50) value of 40 nM and APAS 2.1 μM. The Cibacron Blue molecule was stabilized by four hydrogen bonds and π-π stacking between the anthraquinone ring and Trp104, the ceiling of the active site H-PGDS pocket. Among the four hydrogen bonds, the Cibacron Blue terminal sulphonic group directly interacted with conserved residues Lys112 and Lys198, which recognize the PGH(2) substrate α-chain. In contrast, the APAS anthraquinone ring was inverted to interact with Trp104, while its benzenesulphonic group penetrated the GSH-bound region at the bottom of the active site. Due to the lack of extended aromatic rings, APAS could not directly hydrogen bond with the two conserved lysine residues, thus decreasing the total number of hydrogen bond from four to one. These factors may contribute to the 50-fold difference in the IC(50) values obtained for the two inhibitors.


  • Organizational Affiliation

    Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-Oka, Suita, Osaka 565-0871, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hematopoietic prostaglandin D synthase
A, B, C, D
198Homo sapiensMutation(s): 1 
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
M4M
Query on M4M

Download Ideal Coordinates CCD File 
H [auth C],
K [auth D]
1-amino-9,10-dioxo-4-[(4-sulfamoylphenyl)amino]-9,10-dihydroanthracene-2-sulfonic acid
C20 H15 N3 O7 S2
RRARWTAYDLOASH-UHFFFAOYSA-N
GSH
Query on GSH

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

Download Ideal Coordinates CCD File 
I [auth D]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
G [auth C],
J [auth D]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
M4M PDBBind:  3VI5 IC50: 2100 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.179 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.277α = 95.8
b = 48.986β = 90.99
c = 91.919γ = 90.14
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
d*TREKdata reduction
d*TREKdata 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: 2012-04-18
    Type: Initial release
  • Version 1.1: 2024-03-20
    Changes: Data collection, Database references, Derived calculations