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Fig. 1. Amino acid alignment of chordate cyclooxygenases (labeled by genus). Gaps
(dashes) were introduced to maintain alignment. All amino acids that are
identical or similar to those of the mouse COX2 are shaded (Blosum 62 scoring
matrix with the following amino acid groups considered similar: DN, EQ, ST,
KR, FYW and LIVM). The dimerization domains were well conserved in all the
vertebrates, but not in the urochordate (Ciona). The membrane-binding
domain was well conserved in all species. The catalytic domain begins just
after the second dimerization domain and constitutes about 80% of the protein.
When folded properly, the catalytic domain is further divided into
cyclo-oxygenase and peroxidase active sites. Within the cyclooxygenase site,
active site tyrosine and serine (ASA-acetylated) residues are conserved in all
species (Simmons et al.,
2004). Importantly, the substitution of an isoleucine for a valine
within the cyclooxygenase active site of COX1 only occurs in mammalian COX1.
This substitution allows some drugs to be COX2 specific (Gierse et al.,
1996a), and therefore these drugs would not be expected to discriminate
between COX1 and COX2 of non-mammalian vertebrates. Within the peroxidase
active site, the proximal histidine that binds heme is conserved in all
species. 13–15 amino acids of mouse COX2 that were used as an antigen to
generate antibody 126 are conserved in killifish COX2. GenBank accession
numbers are, from top to bottom: COX2 – Mus (Q05769),
Gallus (P27607), Fundulus (AAS21313), and
Onchorynchus (CAB46017); COX1 – Mus (NP_032995),
Gallus (XP_425326), Onchorynchus (CAC10360) and
Squalus (AAL37727); COXa – Ciona (scaffold 118); COXb
– Ciona (scaffold 207).
