3n8w | pdb_00003n8w

Crystal Structure of R120Q/Native Cyclooxygenase-1 Heterodimer mutant in complex with Flurbiprofen

spinqualitylabelsall models 3n8w, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n8w is a 2 chain structure with sequence from Ovis aries. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.75Å Ligands: BMA, BOG, FLP, HEM, MAN, NAG, NDG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PGH1_SHEEP May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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. See Also Cyclooxygenase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA