GOLPH3 peptide recognition

Investigating the peptide binding site in human GOLPH3 to be used as a pocket targeted by drug-like small molecules

Golgi phosphorylated protein 3 (GOLPH3) is a peripheral membrane protein localized in the Golgi apparatus, regulating the transport of glycosylating enzymes of the glycosphingolipid (GSL) synthetic pathway. The GOLPH3 gene has been found to be overexpressed in various cancers in humans, rendering GOLPH3 an oncoprotein. Despite its clinical importance, there are no inhibitors against this oncoprotein, while at the same time its function remains poorly characterized at a molecular level. Work conducted in our lab and D’Angelo’s lab at EPFL sheds light into the interaction of GOLPH3 with the Golgi membrane and with glycoenzymes of the GSL pathway at a molecular level, providing interesting leads for the design of small molecule inhibitors of the oncogenic activity of GOLPH3.