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PDBsum entry 4oty

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protein ligands Protein-protein interface(s) links
Oxidoreductase/oxidoreductase inhibitor PDB id
4oty
Jmol
Contents
Protein chains
552 a.a.
Ligands
NAG-NAG ×2
NAG ×4
LUR ×2
BOG
Waters ×307
PDB id:
4oty
Name: Oxidoreductase/oxidoreductase inhibitor
Title: Crystal structure of lumiracoxib bound to the apo-mouse- cyclooxygenase-2
Structure: Prostaglandin g/h synthase 2. Chain: a, b. Synonym: cyclooxygenase-2, cox-2, glucocorticoid-regulated inflammatory cyclooxygenase, gripghs, macrophage activation associated marker protein p71/73, pes-2, phs ii, prostaglan synthase 2, pgh synthase 2, pghs-2, prostaglandin-endoperox synthase 2, tis10 protein. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: ptgs2, cox-2, cox2, pghs-b, tis10. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: sf21.
Resolution:
2.35Å     R-factor:   0.181     R-free:   0.221
Authors: S.Xu,M.A.Windsor,S.Banerjee,L.J.Marnett
Key ref: M.A.Windsor et al. (2013). Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib. Bioorg Med Chem Lett, 23, 5860-5864. PubMed id: 24060487 DOI: 10.1016/j.bmcl.2013.08.097
Date:
14-Feb-14     Release date:   26-Feb-14    
Supersedes: 4llz
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q05769  (PGH2_MOUSE) -  Prostaglandin G/H synthase 2
Seq:
Struc:
 
Seq:
Struc:
604 a.a.
552 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.14.99.1  - Prostaglandin-endoperoxide synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
Arachidonate
+ 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  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2013.08.097 Bioorg Med Chem Lett 23:5860-5864 (2013)
PubMed id: 24060487  
 
 
Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib.
M.A.Windsor, P.L.Valk, S.Xu, S.Banerjee, L.J.Marnett.
 
  ABSTRACT  
 
Lumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed a series of lumiracoxib derivatives to identify the structural determinants of substrate-selective inhibition. The hydrogen-bonding potential of the substituents at the ortho positions of the aniline ring dictated the potency and substrate selectivity of the inhibitors. The presence of a 5'-methyl group on the phenylacetic acid ring increased the potency of molecules with a single ortho substituent. Des-fluorolumiracoxib (2) was the most potent and selective inhibitor of endocannabinoid oxygenation. The positioning of critical substituents in the binding site was identified from a 2.35Å crystal structure of lumiracoxib bound to COX-2.