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3n8x, resolution 2.75Å ()
Ligands: , , , ,
Gene: COX1, PTGS1 (Ovis aries)
Activity: Prostaglandin-endoperoxide synthase, with EC number
Related: 3n8v, 3n8w, 3n8y, 3n8z

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


Crystal Structure of Cyclooxygenase-1 in Complex with Nimesulide

Publication Abstract from PubMed

Prostaglandin endoperoxide H synthases (PGHSs)-1 and -2 (also called cyclooxygenases (COXs)-1 and -2) catalyze the committed step in prostaglandin biosynthesis. Both isoforms are targets of nonsteroidal antiinflammatory drugs (NSAIDs). PGHSs are homodimers that exhibit half-of-sites COX activity; moreover, some NSAIDs cause enzyme inhibition by binding only one monomer. To learn more about the cross-talk that must be occurring between the monomers comprising each PGHS-1 dimer, we analyzed structures of PGHS-1 crystallized under five different conditions including in the absence of any tightly binding ligand and in the presence of nonspecific NSAIDs and of a COX-2 inhibitor. When crystallized with substoichiometric amounts of an NSAID, both monomers are often fully occupied with inhibitor; thus, the enzyme prefers to crystallize in a fully occupied form. In comparing the five structures, we only observe changes in the positions of residues 123-129 and residues 510-515. In cases where one monomer is fully occupied with an NSAID and the partner monomer is incompletely occupied, an alternate conformation of the loop involving residues 123-129 is seen in the partially occupied monomer. We propose, on the basis of this observation and previous cross-linking studies, that cross-talk between monomers involves this mobile 123-129 loop, which is located at the dimer interface. In ovine PGHS-1 crystallized in the absence of an NSAID, there is an alternative route for substrate entry into the COX site different than the well-known route through the membrane binding domain.

Comparison of cyclooxygenase-1 crystal structures: cross-talk between monomers comprising cyclooxygenase-1 homodimers., Sidhu RS, Lee JY, Yuan C, Smith WL, Biochemistry. 2010 Aug 24;49(33):7069-79. PMID:20669977

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

About this Structure

3n8x is a 2 chain structure with sequence from Ovis aries. Full crystallographic information is available from OCA.

See Also


  • Sidhu RS, Lee JY, Yuan C, Smith WL. Comparison of cyclooxygenase-1 crystal structures: cross-talk between monomers comprising cyclooxygenase-1 homodimers. Biochemistry. 2010 Aug 24;49(33):7069-79. PMID:20669977 doi:10.1021/bi1003298

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