3hs7

From Proteopedia

Jump to: navigation, search
3hs7, resolution 2.65Å ()
Ligands: , , , , , ,
Gene: Ptgs2, Cox-2, Cox2, Pghs-b, Tis10 (Mus musculus)
Activity: Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1
Related: 1cvu, 1ddx, 1diy, 5cox, 1igx, 3hs5, 3hs6


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

X-ray crystal structure of docosahexaenoic acid bound to the cyclooxygenase channel of cyclooxygenase-2

Publication Abstract from PubMed

The cyclooxygenases (COX-1 and COX-2) are membrane-associated heme-containing homodimers that generate prostaglandin H(2) from arachidonic acid (AA). Although AA is the preferred substrate, other fatty acids are oxygenated by these enzymes with varying efficiencies. We determined the crystal structures of AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) bound to Co(3+)-protoporphyrin IX-reconstituted murine COX-2 to 2.1, 2.4, and 2.65 A, respectively. AA, EPA, and docosahexaenoic acid bind in different conformations in each monomer constituting the homodimer in their respective structures such that one monomer exhibits nonproductive binding and the other productive binding of the substrate in the cyclooxygenase channel. The interactions identified between protein and substrate when bound to COX-1 are conserved in our COX-2 structures, with the only notable difference being the lack of interaction of the carboxylate of AA and EPA with the side chain of Arg-120. Leu-531 exhibits a different side chain conformation when the nonproductive and productive binding modes of AA are compared. Unlike COX-1, mutating this residue to Ala, Phe, Pro, or Thr did not result in a significant loss of activity or substrate binding affinity. Determination of the L531F:AA crystal structure resulted in AA binding in the same global conformation in each monomer. We speculate that the mobility of the Leu-531 side chain increases the volume available at the opening of the cyclooxygenase channel and contributes to the observed ability of COX-2 to oxygenate a broad spectrum of fatty acid and fatty ester substrates.

Structural basis of fatty acid substrate binding to cyclooxygenase-2., Vecchio AJ, Simmons DM, Malkowski MG, J Biol Chem. 2010 Jul 16;285(29):22152-63. Epub 2010 May 12. PMID:20463020

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3hs7 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.

See Also

Reference

  • Vecchio AJ, Simmons DM, Malkowski MG. Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63. Epub 2010 May 12. PMID:20463020 doi:10.1074/jbc.M110.119867

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools