2ZB8

Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and indomethacin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.171 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.

Wu, Y.H.Ko, T.P.Guo, R.T.Hu, S.M.Chuang, L.M.Wang, A.H.J.

(2008) Structure 16: 1714-1723

  • DOI: https://doi.org/10.1016/j.str.2008.09.007
  • Primary Citation of Related Structures:  
    2ZB3, 2ZB4, 2ZB7, 2ZB8

  • PubMed Abstract: 

    PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha,beta-unsaturated double bond of 15-keto-PGE(2), a key step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. Selective inhibition of PTGR2 may contribute to the improvement of insulin sensitivity with fewer side effects. PTGR2 belongs to the medium-chain dehydrogenase/reductase superfamily. The crystal structures reported here reveal features of the NADPH binding-induced conformational change in a LID motif and a polyproline type II helix which are critical for the reaction. Mutation of Tyr64 and Tyr259 significantly reduces the rate of catalysis but increases the affinity to substrate, confirming the structural observations. Besides targeting cyclooxygenase, indomethacin also inhibits PTGR2 with a binding mode similar to that of 15-keto-PGE(2). The LID motif becomes highly disordered upon the binding of indomethacin, indicating plasticity of the active site. This study has implications for the rational design of inhibitors of PTGR2.


  • Organizational Affiliation

    Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Prostaglandin reductase 2357Homo sapiensMutation(s): 0 
Gene Names: PTGR2ZADH1
EC: 1.3.1.48
UniProt & NIH Common Fund Data Resources
Find proteins for Q8N8N7 (Homo sapiens)
Explore Q8N8N7 
Go to UniProtKB:  Q8N8N7
PHAROS:  Q8N8N7
GTEx:  ENSG00000140043 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8N8N7
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.171 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.482α = 90
b = 84.079β = 109.48
c = 73.318γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-09-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description