The structural and molecular basis of substrate specificity of the thioesterases APT1 and APT2

Supervisors: 

Prof Helen Walden, School of Molecular Biosciences (University of Glasgow)

Prof Will Fuller, School of Cardiovascular and Metabolic Health (University of Glasgow)

Dr Luke Chamberlain, Strathclyde Institute of Pharmacy and Biomedical Sciences (University of Strathclyde)

Summary: 

A prominent protein modification found in all eukaryotic species is S-acylation, the attachment of hydrophobic acyl chains onto cysteine side chains. S-Acylation regulates the localisation, stability, interactions, and function of numerous proteins, and thereby affects cellular processes like growth, migration, differentiation, and communication. S-acylation is reversible and is regulated by many zDHHC (on) and APT/ABHD (off) enzymes, however, in contrast to many other enzymes that mediate post-translational regulation of proteins, we currently lack fundamental knowledge about these enzymes and their contribution to cell physiology. This project will provide an important advance in this area by uncovering mechanisms whereby de-S-acylation enzymes recognise their specific substrate partners. The project will provide a broad range of training outcomes including, expertise in cutting-edge molecular and structural analyses, data analysis and team working skills, and networking and presentation skills gained through attendance at relevant conferences. There will also be training in a range of generic areas including research ethics and research integrity, data management, and responsible research.