The N-terminus of COX-1 and its effect on cyclooxygenase-1 catalytic activity  

作　　者：Sean Phipps Michael J. Turner Daniel L. Simmons 

机构地区：[1]Chemistry and Biochemistry Department, Brigham Young University

出　　处：《Journal of Genetics and Genomics》2010年第2期117-123,共7页遗传学报（英文版）

摘　　要：Cyclooxygenases are encoded by COX-1 and COX-2. They share over sixty percent sequence identity in human and are similar to each other in their crystallographic structures. One major difference in the primary structure of these two isozymes is the presence of eight amino acids in the amino-terminal region of COX-1 that are not present in COX-2. The function of this amino acid sequence is unknown. In this study, a human COX-1 mutant （Δ7aa） with this sequence removed was studied in parallel with COX-1. Signal peptide cleavage, N-linked glycosylation, protein expression, distribution and dimerization were not affected by the mutation. The mutant was enzymati-cally active and showed the same sensitivity toward aspirin. The KM for the enzyme remained the same as COX-1. However, the Vmax of the COX-1 mutant decreased by 3.3-fold. We conclude that the COX-1 specific amino-terminal sequence has a subtle but detectable effect on COX-1 catalysis.Cyclooxygenases are encoded by COX-1 and COX-2. They share over sixty percent sequence identity in human and are similar to each other in their crystallographic structures. One major difference in the primary structure of these two isozymes is the presence of eight amino acids in the amino-terminal region of COX-1 that are not present in COX-2. The function of this amino acid sequence is unknown. In this study, a human COX-1 mutant （Δ7aa） with this sequence removed was studied in parallel with COX-1. Signal peptide cleavage, N-linked glycosylation, protein expression, distribution and dimerization were not affected by the mutation. The mutant was enzymati-cally active and showed the same sensitivity toward aspirin. The KM for the enzyme remained the same as COX-1. However, the Vmax of the COX-1 mutant decreased by 3.3-fold. We conclude that the COX-1 specific amino-terminal sequence has a subtle but detectable effect on COX-1 catalysis.

关 键 词：COX-1 COX-2 DIMERIZATION GLYCOSYLATION aspirin KM VMAX 

分 类 号：Q55[生物学—生物化学]