PDBsum entry 3pgh

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Oxidoreductase PDB id
Protein chains
552 a.a. *
NAG ×12
HEM ×4
FLP ×4
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Cyclooxygenase-2 (prostaglandin synthase-2) complexed with a selective inhibitor, flurbiprofen
Structure: Cyclooxygenase-2. Chain: a, b, c, d. Synonym: prostaglandin synthase-2. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Cell_line: cultured sf21. Tissue: dermal. Cell: fibroblast. Cellular_location: endoplasmic reticulum. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Homo-Dimer (from PDB file)
2.50Å     R-factor:   0.236     R-free:   0.316
Authors: R.Kurumbail,W.Stallings
Key ref: R.G.Kurumbail et al. (1996). Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature, 384, 644-648. PubMed id: 8967954
18-Dec-96     Release date:   24-Dec-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q05769  (PGH2_MOUSE) -  Prostaglandin G/H synthase 2
604 a.a.
552 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Prostaglandin-endoperoxide synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
Bound ligand (Het Group name = HEM)
matches with 51.16% similarity
+ AH(2)
+ 2 × O(2)
= prostaglandin H(2)
+ H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   8 terms 
  Biological process     maintenance of blood-brain barrier   64 terms 
  Biochemical function     lipid binding     10 terms  


Nature 384:644-648 (1996)
PubMed id: 8967954  
Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents.
R.G.Kurumbail, A.M.Stevens, J.K.Gierse, J.J.McDonald, R.A.Stegeman, J.Y.Pak, D.Gildehaus, J.M.Miyashiro, T.D.Penning, K.Seibert, P.C.Isakson, W.C.Stallings.
Prostaglandins and glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism. Two isoforms of the membrane protein COX are known: COX-1, which is constitutively expressed in most tissues, is responsible for the physiological production of prostaglandins; and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, is responsible for the elevated production of prostaglandins during inflammation. The structure of ovine COX-1 complexed with several NSAIDs has been determined. Here we report the structures of unliganded murine COX-2 and complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, determined at 3.0 to 2.5 A resolution. These structures explain the structural basis for the selective inhibition of COX-2, and demonstrate some of the conformational changes associated with time-dependent inhibition.

Literature references that cite this PDB file's key reference

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PDB code: 3kk6
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PDB codes: 2zk6 3ads 3adt 3adu 3adv 3adw 3adx
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Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain.
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Novel transthyretin amyloid fibril formation inhibitors: synthesis, biological evaluation, and X-ray structural analysis.
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PDB codes: 3glz 3gs0 3gs4 3gs7
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Leucine/Valine Residues Direct Oxygenation of Linoleic Acid by (10R)- and (8R)-Dioxygenases: EXPRESSION AND SITE-DIRECTED MUTAGENESIS OF (10R)-DIOXYGENASE WITH EPOXYALCOHOL SYNTHASE ACTIVITY.
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A receptor-grounded approach to teaching nonsteroidal antiinflammatory drug chemistry and structure-activity relationships.
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Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors.
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Potent non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase complex.
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Non-redundant functions of cyclooxygenases: oxygenation of endocannabinoids.
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FURSMASA: a new approach to rapid scoring functions that uses a MD-averaged potential energy grid and a solvent-accessible surface area term with parameters GA fit to experimental data.
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Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.
  Nat Chem Biol, 4, 700-707.
PDB codes: 3e65 3e67 3e68 3e6l 3e6n 3e6o 3e6t 3e7g 3e7i 3e7m 3e7s 3e7t 3eah 3eai 3ebd 3ebf 3ej8
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Shapelets: possibilities and limitations of shape-based virtual screening.
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An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies.
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A ligand's-eye view of protein binding.
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LysM domains from Pteris ryukyuensis chitinase-A: a stability study and characterization of the chitin-binding site.
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Effect of a nonprotein bioactive agent on the reduction of cyclooxygenase-2 and tumor necrosis factor-alpha in human intervertebral disc cells in vitro.
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Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.
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PDB codes: 2zb3 2zb4 2zb7 2zb8
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Molecular determinants for the selective inhibition of cyclooxygenase-2 by lumiracoxib.
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18159230 A.Peretz, N.Degani-Katzav, M.Talmon, E.Danieli, A.Gopin, E.Malka, R.Nachman, A.Raz, D.Shabat, and B.Attali (2007).
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Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-alpha-substituted indomethacin ethanolamides.
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PDB codes: 2oye 2oyu
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Cyclooxygenase (COX) inhibitors and the intestine.
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Expression of recombinant G-protein coupled receptors for structural biology.
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Clinical pharmacology of celecoxib, a COX-2 selective inhibitor.
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A critical role of non-active site residues on cyclooxygenase helices 5 and 6 in the control of prostaglandin stereochemistry at carbon 15.
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A generalized born implicit-membrane representation compared to experimental insertion free energies.
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Selective COX-2 inhibitors, eicosanoid synthesis and clinical outcomes: a case study of system failure.
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Design, synthesis and pharmacological evaluation of 4-[2-alkylthio-5(4)-(4-substitutedphenyl)imidazole-4(5)yl]benzenesulfonamides as selective COX-2 inhibitors.
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17202703 N.Handler, W.Jaeger, H.Puschacher, K.Leisser, and T.Erker (2007).
Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.
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Design, Syntheses, Biological Evaluation, and Docking Studies of 2-Substituted 5-Methylsulfonyl-1-Phenyl-1H-Indoles: Potent and Selective in vitro Cyclooxygenase-2 Inhibitors.
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PDB code: 1bl4
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PDB codes: 1amv 2amv
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