Cyclooxygenase-2 dimerization activity may be influenced by its monomers’ glycosylation at Asn580
Location
Guzman 202
Start Date
4-19-2018 2:30 PM
End Date
4-19-2018 3:00 PM
Student Type
Undergraduate - Honors
Faculty Mentor(s)
Randall Hall, Ph.D.
Presentation Format
Oral Presentation
Abstract/Description
Cyclooxygenases (COXs) are enzymes that aid in synthesizing prostaglandins, lipid-based cell signals involved in a variety of physiological functions including platelet formation, inflammation, blood flow, and labor induction. Two forms of COX exist, COX-1 & COX-2, but overexpression of the COX-2 enzyme has been shown to play a role in several diseases, including arthritis and certain cancers. COX-2 functions as a dimer, and each monomer contains a variable glycosylation site at asparagine 580 (Asn580). Past studies have shown that glycosylation at this site affects both the turnover of the COX-2 protein as well as the efficacy of several COX-2 inhibitors. In this study, our overall goal is to predict if glycosylation at Asn580 impedes or enhances COX-2 dimerization. We have used molecular dynamics and free energy perturbation theory (FEP) as well as computer-modeling software NAMD to simulate the thermodynamics of COX-2 dimerization with and without glycosylation at Asn580. Results indicate that COX-2 is approximately 10-5 less likely to dimerize when both monomers are glycosylated at Asn580.
Cyclooxygenase-2 dimerization activity may be influenced by its monomers’ glycosylation at Asn580
Guzman 202
Cyclooxygenases (COXs) are enzymes that aid in synthesizing prostaglandins, lipid-based cell signals involved in a variety of physiological functions including platelet formation, inflammation, blood flow, and labor induction. Two forms of COX exist, COX-1 & COX-2, but overexpression of the COX-2 enzyme has been shown to play a role in several diseases, including arthritis and certain cancers. COX-2 functions as a dimer, and each monomer contains a variable glycosylation site at asparagine 580 (Asn580). Past studies have shown that glycosylation at this site affects both the turnover of the COX-2 protein as well as the efficacy of several COX-2 inhibitors. In this study, our overall goal is to predict if glycosylation at Asn580 impedes or enhances COX-2 dimerization. We have used molecular dynamics and free energy perturbation theory (FEP) as well as computer-modeling software NAMD to simulate the thermodynamics of COX-2 dimerization with and without glycosylation at Asn580. Results indicate that COX-2 is approximately 10-5 less likely to dimerize when both monomers are glycosylated at Asn580.