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PDBsum entry 3mdl

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
3mdl
Jmol
Contents
Protein chains
552 a.a.
Ligands
1AG ×2
AKR ×5
GOL ×3
COH ×2
NAG-NAG ×3
NAG-NAG-MAN
NAG ×2
BOG
Waters ×960
PDB id:
3mdl
Name: Oxidoreductase
Title: X-ray crystal structure of 1-arachidonoyl glycerol bound to cyclooxygenase channel of cyclooxygenase-2
Structure: Prostaglandin g/h synthase 2. Chain: a, b. Fragment: unp residues 20 to 599. Synonym: cyclooxygenase-2, cox-2, prostaglandin-endoperoxid 2, prostaglandin h2 synthase 2, pgh synthase 2, pghs-2, phs glucocorticoid-regulated inflammatory cyclooxygenase, gripg protein, macrophage activation-associated marker protein p7 2. Engineered: yes.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: ptgs2, cox-2, cox2, pghs-b, tis10. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.20Å     R-factor:   0.168     R-free:   0.215
Authors: A.J.Vecchio,M.G.Malkowski
Key ref: A.J.Vecchio and M.G.Malkowski (2011). The structural basis of endocannabinoid oxygenation by cyclooxygenase-2. J Biol Chem, 286, 20736-20745. PubMed id: 21489986 DOI: 10.1074/jbc.M111.230367
Date:
30-Mar-10     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 = 1AG)
matches with 81.48% similarity
+ AH(2)
+ 2 × O(2)
=
prostaglandin H(2)
Bound ligand (Het Group name = COH)
matches with 51.11% similarity
+
+ 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.M111.230367 J Biol Chem 286:20736-20745 (2011)
PubMed id: 21489986  
 
 
The structural basis of endocannabinoid oxygenation by cyclooxygenase-2.
A.J.Vecchio, M.G.Malkowski.
 
  ABSTRACT  
 
The cyclooxygenases (COX-1 and COX-2) oxygenate arachidonic acid (AA) in the committed step of prostaglandin biogenesis. Substitutions of I434V, H513R, and I523V constitute the only differences in residues lining the cyclooxygenase channel between COX-1 and COX-2. These changes create a hydrophobic pocket in COX-2, with Arg-513 located at the base of the pocket, which has been exploited in the design of COX-2-selective inhibitors. Previous studies have shown that COX-2, but not COX-1, can oxygenate endocannabinoid substrates, including 2-arachidonoyl glycerol (2-AG). To investigate the isoform-specific structural basis of endocannabinoid binding to COX-2, we determined the crystal structure of the 2-AG isomer 1-arachidonoyl glycerol (1-AG) in complex with wild type and R513H murine (mu) COX-2 to 2.2 and 2.35 Å, respectively, and R513H muCOX-2 in complex with AA to 2.45 Å resolution. The 2,3-dihydroxypropyl moiety of 1-AG binds near the opening of the cyclooxygenase channel in the space vacated by the movement of the Leu-531 side chain, validating our previous hypothesis implicating the flexibility of the Leu-531 side chain as a determinant for the ability of COX-2 to oxygenate endocannabinoid substrates. Functional analyses carried out to compliment our structural findings indicated that Y355F and R513H muCOX-2 constructs had no effect on the oxygenation of 1-AG and 2-AG, whereas substitutions that resulted in a shortened side chain for Leu-531 had only modest effects. Both AA and 1-AG bind to R513H muCOX-2 in conformations similar to those observed in the co-crystal structures of these substrates with wild type enzyme.