Computational Chemistry: Electrophilic Attacks on the Thioester Linkage of Ubiquitin
Poster Number
1C
Format
Poster Presentation
Faculty Mentor Name
Anthony Dutoi
Faculty Mentor Department
Chemistry
Abstract/Artist Statement
Ubiquitin is a protein found in eukaryotes that has functions in protein homeostasis, including degradation and enzyme regulation. It carries out these functions by tagging other molecules and forming chains of ubiquitin molecules that are used to indicate the various tags. The process by which ubiquitin tags other proteins is facilitated by three proteins–E1, E2, and E3–that allow for the transfer of ubiquitin onto the target molecule. This transfer involves the amine end of a lysine on the target protein and the thioester linkage of a ubiquitin–E2 complex. However, the mechanism of the final transfer of ubiquitin is mostly unknown, such as the geometry of the ubiquitin-E2 complex and the enzymatic catalysis involved. We used quantum computational calculations to observe the conformations of the protein complex and to analyze the energy of catalysis. By adjusting the dihedral angles of the glycine residue and the distance of lysine on the target protein, we were able to analyze the varying energies to observe any peaks in energy due to enzymatic activity. It was concluded that there was no dependence in energy found from adjusting the dihedral angles of glycine. Therefore, glycine torsions may have no effect on the increase of the enzymatic activity that could be responsible for ubiquitin tagging.
Location
Information Commons, William Knox Holt Memorial Library and Learning Center
Start Date
29-4-2023 10:00 AM
End Date
29-4-2023 1:00 PM
Computational Chemistry: Electrophilic Attacks on the Thioester Linkage of Ubiquitin
Information Commons, William Knox Holt Memorial Library and Learning Center
Ubiquitin is a protein found in eukaryotes that has functions in protein homeostasis, including degradation and enzyme regulation. It carries out these functions by tagging other molecules and forming chains of ubiquitin molecules that are used to indicate the various tags. The process by which ubiquitin tags other proteins is facilitated by three proteins–E1, E2, and E3–that allow for the transfer of ubiquitin onto the target molecule. This transfer involves the amine end of a lysine on the target protein and the thioester linkage of a ubiquitin–E2 complex. However, the mechanism of the final transfer of ubiquitin is mostly unknown, such as the geometry of the ubiquitin-E2 complex and the enzymatic catalysis involved. We used quantum computational calculations to observe the conformations of the protein complex and to analyze the energy of catalysis. By adjusting the dihedral angles of the glycine residue and the distance of lysine on the target protein, we were able to analyze the varying energies to observe any peaks in energy due to enzymatic activity. It was concluded that there was no dependence in energy found from adjusting the dihedral angles of glycine. Therefore, glycine torsions may have no effect on the increase of the enzymatic activity that could be responsible for ubiquitin tagging.