Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

Structural basis for catalytic activation by the human ZNF451 SUMO E3 ligase.

Abstract: E3 protein ligases enhance transfer of ubiquitin-like (Ubl) proteins from E2 conjugating enzymes to substrates by stabilizing the thioester-charged E2~Ubl in a closed configuration optimally aligned for nucleophilic attack. Here, we report biochemical and structural data that define the N-terminal domain of the Homo sapiens ZNF451 as the catalytic module for SUMO E3 ligase activity. The ZNF451 catalytic module contains tandem SUMO-interaction motifs (SIMs) bridged by a Pro-Leu-Arg-Pro (PLRP) motif. The first SIM and PLRP motif engage thioester-charged E2~SUMO while the next SIM binds a second molecule of SUMO bound to the back side of E2. We show that ZNF451 is SUMO2 specific and that SUMO modification of ZNF451 may contribute to activity by providing a second molecule of SUMO that interacts with E2. Our results are consistent with ZNF451 functioning as a bona fide SUMO E3 ligase.

Fully synthetic carbohydrate HIV antigens designed on the logic of the 2G12 antibody.

Abstract: Di- and trivalent glycopeptide mimics of the HIV 2G12 epitope have been synthesized and evaluated for their comparative 2G12 binding characteristics. The epitope mimics consist of a cyclic peptide scaffold (unrelated to gp120 peptide sequences) attached via aspartate linkages to two or three copies of the high-mannose glycan, Man9GlcNAc2. The synthesis has been achieved via high-yielding double and triple Lansbury aspartylations of Man9GlcNAc2-NH2 with peptides containing, respectively, two and three aspartate residues. Conjugation of such constructs with an immunogenic carrier protein, OMPC, has been accomplished through the peptide's cysteine sulfhydryl function, and Biacore assays have shown that binding affinity for 2G12 increases with increasing valency.