1. Volume 16, Issue 11, Pages 1714-1723 (November 2008)
Structural Basis for Catalytic and Inhibitory Mechanisms of Human Prostaglandin Reductase PTGR2 
Yu-Hauh Wu, Tzu-Ping Ko, Rey-Ting Guo, Su-Ming Hu, Lee-Ming Chuang, Andrew H.-J. Wang 
Structure 
Volume 16, Issue 11, Pages (November 2008)
DOI: /j.str
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2. Figure 1 Enzymatic Reduction of 15-Keto-PGE2 by PTGR2
(A) The chemical reactions catalyzed by 15-PGDH and PTGR2.
(B) The chemical structure of nicotinamide (NCA).
(C) The chemical structure of indomethacin (IMN).
Structure  , DOI: ( /j.str )
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3. Figure 2 Structure-Based Sequence Alignment of PTGR2 and Homologs
(A) Stereo view of the crystal structure of the hPTGR2-NADP+-15-keto-PGE2 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-PGE2 (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/LTB4DH (Q9EQZ5), and human 13-PGR/LTB4DH (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.
Structure  , DOI: ( /j.str )
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4. Figure 3
Overall Structural Comparison of Human PTGR2 with a Homolog from the MDR Superfamily
The structure is shown in stereo. Coloring for hPTGR2 is as in Figure 2A except for the LID and PPII helix (blue). Guinea pig 13-PGR/LTB4DH is colored in gray (PDB ID code 1V3V). NADP+ and the ω chain of 15-keto-PGE2 in 13-PGR/LTB4DH are also shown (gray carbons).
Structure  , DOI: ( /j.str )
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5. Figure 4
Conformational Changes of the LID Motif and PPII Helix upon NADPH Binding
(A) Stereo view of the coenzyme-binding pocket. Residues from the nucleotide-binding domain and catalytic domain are colored in cyan and magenta, respectively. Hydrogen bonds are indicated with dotted lines.
(B) Structural comparison of the mPTGR2 (cyan) binary complex (NADPH in yellow) and mtPTGR2 apoenzyme (light purple) (PDB ID code 1VJ1) shown in a stereo view. The nucleotide-binding loop (Gly254–Tyr265) of mtPTGR2 is disordered. The PPII helices of mPTGR2 and mtPTGR2 are shown in blue and magenta, respectively.
Structure  , DOI: ( /j.str )
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6. Figure 5 Binding Mode of 15-Keto-PGE2
(A) Molecular surface representation of the substrate-binding pocket. NADP+ (gray carbons) and 15-keto-PGE2 (green carbons) are shown. The C4 of nicotinamide is highlighted in yellow.
(B) Substrate-binding pocket. The 1.63 Å 2Fo − Fc electron density map (orange) of 15-keto-PGE2 is contoured at the level of 1σ. Residues lining the pocket are shown in stick models (yellow carbons). Water molecules are displayed as marine balls.
Structure  , DOI: ( /j.str )
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7. Figure 6 Putative Catalytic Residues
Alignment of the active sites of hPTGR2 (cyan), mPTGR2 (magenta), 13-PGR/LTB4DH (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/LTB4DH.
Structure  , DOI: ( /j.str )
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8. Figure 7 A Possible Catalytic Mechanism for PTGR2
R: the adenosine diphosphate group of NADP(H). R1: C17–C20 of the 15-keto-PGE2 ω chain. R2: C1–C7 and the C1-carboxylate group of the 15-keto-PGE2 α chain. X: the aromatic side chain of Tyr64 or a hydrogen of water. Hydrogen bonds are indicated by dashed lines.
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9. Figure 8
Nicotinamide and Indomethacin Binding in the Substrate-Binding Pocket
(A) NCA binding mode. The 1.8 Å 2Fo − Fc electron density map of NCA is contoured at the 1σ level.
(B) NCA (gray carbons) assumes a binding orientation similar to the α,β-unsaturated ketone moiety of 15-keto-PGE2 (green carbons). Amino acid residues in hPTGR2-NADPH-NCA and hPTGR2-NADP+-15-keto-PGE2 are in yellow and marine, respectively.
(C) IMN binding mode. The 2.0 Å 2Fo − Fc electron density map of IMN is contoured at the 1σ level.
(D) Superposition of active sites of hPTGR2-NADP+-IMN (yellow residues) and hPTGR2-NADP+-15-keto-PGE2 (marine residues) structures.
Structure  , DOI: ( /j.str )
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