(491.5) Ligands Binding Peptidoglycan-Associated Lipoprotein as Biomarkers for Sepsis

Poster Board Number: A113

Isabelle Pilo (Rochester Institute of Technology), Lea Michel (Rochester Institute of Technology), Andrew Torelli (Ithaca College), Jared French (University of Minnesota), Katherine Hicks (SUNY Cortland), Kayla Lawrence (SUNY Cortland), Ashton Ariola (University of Minnesota), Conner Woods (North Park University), Anais Rhodes (Hampton University)

Peptidoglycan-Associated Lipoprotein (Pal) is an outer membrane protein conserved among Gram-negative bacteria. Pal protein binds to peptidoglycan and several outer membrane and periplasmic proteins as part of the Pal-Tol complex, a system of interacting proteins that link together the outer membrane, the peptidoglycan layer, and the inner membrane. The Pal-Tol complex is important for maintaining the integrity of the cell envelope and plays a role in the invagination process during cell division. We proposed to identify small molecules that could disrupt the Pal-TolB interaction and/or Pal-peptidoglycan binding, as the two binding sites are thought to overlap. As part of a summer research program, funded by the NSF, our team of researchers used the computational program Dock6 to dock a variety of small molecules from the ZINC database in different rigid and flexible conformations. The small molecules that docked the most favorably were linear polycyclic structures that had alcohol and amine groups, such as FMN, capastat, leucal, and ceftriaxone. We also describe our ongoing efforts to develop a binding assay to test the effect of these small molecules on Pal-TolB and Pal-peptidoglycan binding. Due to Pal’s role in cell division and cell envelope integrity, we propose that small molecules that disrupt interactions to Pal’s binding partners could serve as potential antibiotics.

Rochester Institute of Technology and REU Site: Molecular Interactions Virtual REU, NSF Award # 2051087