Presentation Title

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

Department

Natural Sciences and Mathematics

Student Type

Undergraduate - Honors

Faculty Mentor

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.

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Apr 19th, 2:30 PM Apr 19th, 3:00 PM

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.