Isolation and covalent structure of the aspirin-modified, active-site region of prostaglandin synthetase.
Aspirin (acetylsalicylic acid) inhibits prostaglandin synthesis by acetylating a single internal serine residue of the initial enzyme in the biosynthetic pathway, prostaglandin synthetase. In this study, the region of the enzyme that is modified by aspirin has been isolated, and its amino acid sequence has been determined. Sheep vesicular gland [acetyl-3H]prostaglandin synthetase was purified following treatment with [acetyl-3H]aspirin and digest with pepsin. An acetyl-3H-labeled peptic peptide of approximately 25 residues was isolated by high-pressure liquid chromatography, and its amino acid sequence was determined to be Ile-Glu-Met-Gly-Ala-Pro-Phe-Ser-Leu-Lys-Gly-Leu-Gly-Asn-Pro-Ile-Glu-Ser-Pro-Glu-Tyr. The acetylated serine residue was located at position 8 in this sequence. The current study marks this polypeptide sequence as a region related to an active site of the enzyme.
D000595:Amino Acid Sequence; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001665:Binding Sites; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010434:Pepsin A; D010446:Peptide Fragments / Q000302:isolation & purification; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011485:Protein Binding; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D014357:Trypsin
D010446:Peptide Fragments; D011451:Prostaglandin-Endoperoxide Synthases; D014357:Trypsin; D010434:Pepsin A; D001241:Aspirin