Ministry of Education

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Peptide Ligase: Molecular Gluer for Proteins (2017)

Our CoS team:
Lead PI: Prof James P Tam (SBS)
Co-PIs: Assoc Prof Julien Lescar (SBS), Assoc Prof Liu Chuan Fa (SBS); Assoc Prof Sze Siu Kwan (SBS);
                                                  
 
James Tam, Julien Lescar, Liu Chuan Fa, Sze Siu Kwan.png
James Tam              Julien Lescar               Liu Chuan Fa             Sze Siu Kwan
 
Our program focuses on a new family of enzymes known as peptide ligases and the rules to design ligases from proteases. The knowledge gained will provide fundamental insights to engineer novel synthetic ligases as catalytic “molecular staplers” for bonding chemicals, proteins, polymers and inorganic materials with unique site-specificity and exquisite efficiency. In turn, these advances will influence research and development of biochemical, medical, pharmaceutical, food and material sciences.
Enzymes, which catalyze >5,000 types of reactions, are bio-transformers and engines of life. They are also enabling tools for research and useful commodities for industrial applications. Proteases, enzymes which break peptide bonds, are ubiquitous, with >400,000 found in databases and >4200 characterized. In contrast, peptide or protein ligases, peptide-bond-forming enzymes, which catalyze the reverse reactions of proteases are poorly characterized (Figure 1). Many are ATP-dependent and exist as protein complexes. Consequently, they are not applicable for biochemical uses in cell-free systems. Stand-alone and “ATP-independent” peptide ligases are the enzymes that would be highly useful for in-vitro biochemical reactions, but they are exceedingly rare. Thus far, only a few such ligases have been characterized. Hence, the discovery and the ability to engineer “ATP-independent peptide ligases” offer many exciting new possibilities and an open-ended research program to explore new frontiers in science and engineering.



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