Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V53
Höfundar / Authors: Yiming Yang Jonatansdottir, Jens Guðmundur Hjörleifsson
Starfsvettvangur / Affiliations: University of Iceland, Faculty of Physical Sciences
Kynnir / Presenter: Yiming Yang Jónatansdóttir
GPI is a moonlighting protein that displays multiple functions across different cell types, within and outside the cell. In the cytoplasm, GPI acts as an enzyme, catalyzing the 2nd step of glycolysis, serving as a metabolic switch between glycolysis and the pentose phosphate pathway. When being secreted into extracellular space, it can take on several roles and terms, one of which is the autocrine motility factor (AMF) – a cytokine that stimulates tumor cell survival, migration, and invasion through receptor-mediated signaling pathways. Noteworthily, the cytokine activity of GPI/AMF is reportedly inhibited by sugar phosphates that bind to the enzyme active site, suggesting an overlap of GPI’s enzymatic and cytokine functions. This dual role, combined with the potential to suppress both activities using a single inhibitor, positions GPI at the intersection of cancer metabolism and signaling, making it attractive candidate for therapeutic intervention. This study aims to identify compounds that inhibit the enzymatic activity of GPI. To this end, we have carried out a structure-based virtual screening using Schrödinger’s Glide docking platform, evaluating large chemical libraries against the active site of GPI. The most promising hits are proposed for experimental validation in biochemical assays, with the ultimate goal of introducing a new class of dual-function GPI/AMF inhibitors for cancer therapy.