A stickier version of nature's glue

In drug development, peptides used as chemotherapy drugs and cancer cell-specific antibodies are joined together with the help of enzymes known as peptide ligases. Previously, Prof James Tam and his team from NTU’s School of Biological Sciences discovered a highly efficient peptide ligase in the blue pea plant, Clitoria ternatea, which is a medicinal plant native to Singapore.

Working together with structural biologist Assoc Prof Julien Lescar and chemical biologist Assoc Prof Liu Chuan Fa, the researchers have now deduced the enzyme’s structure at 2.4 angstrom (0.24 nanometers) resolution. From the crystal structure, they discovered two specific regions in the molecule that are crucial for the accuracy and speed of the enzymatic reaction.

They used these insights to genetically engineer enzymes with increased ligase activity and converted a closely related enzyme with protease (protein-cleaving) activity into a ligase.

Defining the molecular structures important for enzymatic activity will facilitate identification of useful peptide ligases in plants, and help in the design of new enzymes for use in biotechnology and drug development, Prof Tam says.

The article “Structural determinants for peptide-bond formation by asparaginyl ligases” was published in Proceedings of the National Academy of Sciences of the USA (2019), DOI: 10.1073/ pnas.1818568116.

The article appeared first in NTU’s research & innovation magazine Pushing Frontiers (issue #16, February 2020).