PDBsum entry 2zb8

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protein ligands links
Oxidoreductase PDB id
Protein chain
342 a.a. *
SO4 ×2
Waters ×478
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of human 15-ketoprostaglandin delta-13- reductase in complex with NADP and indomethacin
Structure: Prostaglandin reductase 2. Chain: a. Synonym: ptgr2, 15-oxoprostaglandin 13-reductase, zinc- binding alcohol dehydrogenase domain-containing protein 1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptgr2, zadh1. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.171     R-free:   0.218
Authors: Y.H.Wu,A.H.J.Wang,T.P.Ko,R.T.Guo,S.M.Hu,L.M.Chuang
Key ref:
Y.H.Wu et al. (2008). Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2. Structure, 16, 1714-1723. PubMed id: 19000823 DOI: 10.1016/j.str.2008.09.007
16-Oct-07     Release date:   30-Sep-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q8N8N7  (PTGR2_HUMAN) -  Prostaglandin reductase 2
351 a.a.
342 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 15-oxoprostaglandin 13-oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 11-alpha-hydroxy-9,15-dioxoprost-5-enoate + NAD(P)(+) = (5Z)-(13E)-11- alpha-hydroxy-9,15-dioxoprosta-5,13-dienoate + NAD(P)H
Bound ligand (Het Group name = NAP)
corresponds exactly
= (5Z)-(13E)-11- alpha-hydroxy-9,15-dioxoprosta-5,13-dienoate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     13-prostaglandin reductase activity     4 terms  


    Added reference    
DOI no: 10.1016/j.str.2008.09.007 Structure 16:1714-1723 (2008)
PubMed id: 19000823  
Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.
Y.H.Wu, T.P.Ko, R.T.Guo, S.M.Hu, L.M.Chuang, A.H.Wang.
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.
  Selected figure(s)  
Figure 2.
Figure 2. Structure-Based Sequence Alignment of PTGR2 and Homologs
(A) Stereo view of the crystal structure of the hPTGR2-NADP^+-15-keto-PGE[2] complex. The nucleotide-binding domain (H149–Y292) and catalytic domain (M1-G148; K293–L351) are colored in purple and orange, respectively. The NADP^+ (yellow carbons), 15-keto-PGE[2] (green carbons), and sulfate ions (dark yellow sulfurs) are shown as ball-and-stick models.
(B) Multiple sequence alignments of human PTGR2 (SwissProt entry Q8N8N7), mouse PTGR2 (Q3TG36), guinea pig 13-PGR/LTB[4]DH (Q9EQZ5), and human 13-PGR/LTB[4]DH (A8K0N2). The LID motifs and PPII helices of PTGR2 are indicated by double-headed arrows. The conserved nucleotide-binding motif is underlined. Tyr64 and Tyr259 are marked with red boxes.
Figure 6.
Figure 6. Putative Catalytic Residues
Alignment of the active sites of hPTGR2 (cyan), mPTGR2 (magenta), 13-PGR/LTB[4]DH (yellow), and Etr1p (gray). Hydrogen bonds in PTGR2 and Etr1p are in red and blue, respectively. Tyr262(B) is from the countersubunit B of 13-PGR/LTB[4]DH.
  The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 1714-1723) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20835842 S.Porté, A.Moeini, I.Reche, N.Shafqat, U.Oppermann, J.Farrés, and X.Parés (2011).
Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin.
  Cell Mol Life Sci, 68, 1065-1077.  
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