Sandbox Reserved 1471: Difference between revisions
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== Structure == | == Structure == | ||
[[Image:Heteroatoms of COX2.jpg|thumb|Figure 1: Ligands (green) bound to COX-2. Image taken in Chimera from PDB file 5KIR.]] | [[Image:Heteroatoms of COX2.jpg|thumb|Figure 1: Ligands (green) bound to COX-2. Image taken in Chimera from PDB file 5KIR.]] | ||
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== Energetics == | == Energetics == | ||
Arachidonic acid has a higher kcat value of 27.0 ± 0.4 s-1 and a lower Km value of 5.14 ± 0.29 µM than EPA and DHA for the affinity to COX-2.(Vicchio) This means that arachidonic acid is the preferred substrate for COX-2 when compared with EPA and DHA fatty acids. The rate of the reaction can depend on the concentration of the substrate. However, the rate can be slowed or stopped with an inhibitor. <scene name='80/800650/Human_cox-2_bound_to_vioxx/3'>Rofecoxib</scene> and Celecoxib are two inhibitors that have selectivity towards COX-2. (Orlando) They differ from the nonsteroidal anti-inflammatory drugs (NSAIDs) because of their selectivity for COX-2.(Orlando) NSAIDs inhibit both COX-1 and COX-2.(Orlando) Rofecoxib, commonly known as Vioxx, has a 1000-fold selectivity for COX-2 over COX-1. (Chan) It also has a 60-fold selectivity for COX-2 when compared to the selectivity of Celecoxib (Celebrex) for COX-2. (Orlando) The difference in the kinetics of Rofecoxib and Celecoxib is speculated to be from the binding kinetics and not the interaction between the inhibitor and the enzyme.(Orlando) The rate constant for the inhibition of COX-2 by Rofecoxib was experimentally determined to be 0.0036 ± 0.0024 µM-1s-1 for a two-step mechanism.(Chan) When bound to COX-2, Rofecoxib makes 42 contacts with the nearby residues where it binds.(Orlando) Celecoxib differs from Rofecoxib in structure by having a “pyrazole heterocycle and a sulfonamide moiety” whereas Rofecoxib has a “furanone heterocycle and a methyl sulfone moiety.”(Orlando) | |||
