Cyclooxygenases (COX-1 and COX-2) are heme-containing, membrane-bound proteins that share a high degree of sequence identity and also have very similar active site topog-raphy.138,143-145 Note that the homologous residues of the COX-2 isozyme are numbered in parallel with the similar amino acid residues found at the active site of COX-1 isozyme for easier comparison of their structural differences in the following discussion (i.e., the actual Arg-106 of human COX-2 [hCOX-2] is numbered as Arg-120).143 The actual hCOX-2 assignments for these residues are provided in parentheses.
Thus, despite their similarity, the active site for hCOX-2 is approximately 20% larger than the COX-1 binding site because of the replacement of Ile-523 in COX-1 with a smaller Val-523 in hCOX-2 (Val-509).138 144 145 There are a total of 24 amino acid residues lining the largely hy-drophobic AA binding site with only one difference between the isozymes (i.e., Ile-523 in COX-1 and Val-509 in hCOX-2). The hCOX-2 isozyme has an additional hy-drophilic side pocket accessible for drug binding, extended from the main binding pocket.143 The size and nature of this hydrophilic side pocket for binding in hCOX-2 is a result of further substitutions Ile-434 and His-513 in COX-1 with a smaller Val-434 (Val 420 in hCOX-2) and a more basic Arg-513 (Arg-499 in hCOX-2).146 Thus, it is not surprising that this basic amino acid residue in hCOX-2 (Arg-499) may provide an additional binding interaction for selective COX-2 inhibitors such as celecoxib.144 Although there is only a very limited amount of published data showing how the substrate, AA, binds to cyclooxygenases, the relative positioning of the double bonds in AA at the active site, proposed by Gund and Shen based on the conformational analysis of indomethacin and other conventional NSAIDs, is still currently valid.147
Interestingly, Arg-120 (Arg-104 in hCOX-2) is the only positively charged amino acid residue in the COX active site, on one end of the active site as depicted by Luong144,148 and is responsible for binding, via an ionic interaction, with the carboxylate anion of the substrate
(AA) or the conventional NSAIDs. The amino acid residue Tyr-385 (Tyr-371 in hCOX-2) is located on the opposite end of the COX active site and is believed to serve as the catalytic residue for activating molecular oxygen and its initial addition to the A11-double bond of the substrate to form PGG2.143-148 Furthermore, the presence of an amino acid residue, Ser-530 (Ser-516 in hCOX-2) is believed to be involved only in the irreversible inactiva-tion by aspirin and NSAID action but not contributing to any substrate binding.143
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What exactly is a detox routine? Basically a detox routine is an all-natural method of cleansing yourbr body by giving it the time and conditions it needs to rebuild and heal from the damages of daily life and the foods you eat and other substances you intake. There are many different types of known detox routines.