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PDBsum entry 3qh0

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
3qh0
Jmol
Contents
Protein chains
552 a.a.
Ligands
EDO ×23
PLM
AKR ×2
COH ×2
HSQ-NAG
NAG-NAG-MAN
NAG ×2
BOG
NAG-NDG
NAG-NAG
Waters ×753
PDB id:
3qh0
Name: Oxidoreductase
Title: X-ray crystal structure of palmitic acid bound to the cycloo channel of cyclooxygenase-2
Structure: Prostaglandin g/h synthase 2. Chain: a, b. Fragment: unp residue 1-608. 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: cox-2, cox2, pghs-b, ptgs2, tis10. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.10Å     R-factor:   0.161     R-free:   0.199
Authors: A.J.Vecchio,M.G.Malkowski
Key ref: L.Dong et al. (2011). Human cyclooxygenase-2 is a sequence homodimer that functions as a conformational heterodimer. J Biol Chem, 286, 19035-19046. PubMed id: 21467029 DOI: 10.1074/jbc.M111.231969
Date:
25-Jan-11     Release date:   13-Apr-11    
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
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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
Bound ligand (Het Group name = COH)
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  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M111.231969 J Biol Chem 286:19035-19046 (2011)
PubMed id: 21467029  
 
 
Human cyclooxygenase-2 is a sequence homodimer that functions as a conformational heterodimer.
L.Dong, A.J.Vecchio, N.P.Sharma, B.J.Jurban, M.G.Malkowski, W.L.Smith.
 
  ABSTRACT  
 
Prostaglandin endoperoxide H synthases 1 and 2, also known as cyclooxygenases (COXs) 1 and 2, convert arachidonic acid (AA) to prostaglandin endoperoxide H(2). Prostaglandin endoperoxide H synthases are targets of nonspecific nonsteroidal anti-inflammatory drugs and COX-2-specific inhibitors called coxibs. PGHS-2 is a sequence homodimer. Each monomer has a peroxidase and a COX active site. We find that human PGHS-2 functions as a conformational heterodimer having a catalytic monomer (E(cat)) and an allosteric monomer (E(allo)). Heme binds tightly only to the peroxidase site of E(cat), whereas substrates, as well as certain inhibitors (e.g. celecoxib), bind the COX site of E(cat). E(cat) is regulated by E(allo) in a manner dependent on what ligand is bound to E(allo). Substrate and nonsubstrate fatty acids (FAs) and some COX inhibitors (e.g. naproxen) preferentially bind to the COX site of E(allo). AA can bind to E(cat) and E(allo), but the affinity of AA for E(allo) is 25 times that for E(cat). Palmitic acid, an efficacious stimulator of human PGHS-2, binds only E(allo) in palmitic acid/murine PGHS-2 co-crystals. Nonsubstrate FAs can potentiate or attenuate actions of COX inhibitors depending on the FA and whether the inhibitor binds E(cat) or E(allo). Our studies suggest that the concentration and composition of the free FA pool in the environment in which PGHS-2 functions in cells, the FA tone, is a key factor regulating PGHS-2 activity and its responses to COX inhibitors. We suggest that differences in FA tone occurring with different diets will likely affect both base-line prostanoid synthesis and responses to COX inhibitors.