Research from the University of Zaragoza determines the keys to the mechanism of action of an enzyme involved in cancer

The journal Nature Communications publishes the achievements of the group of Ramón Hurtado-Guerrero, ARAID researcher at the BIFI institute, together with Ana A. García and Laura Ceballos and other researchers nationwide

Malfunction of this enzyme is related to a wide spectrum of types of cancer.

Knowing its structure and mechanism of action is essential to develop drugs specifically directed against this enzyme.

The journal Nature Communications has just published research from the University of Zaragoza that determines the keys to the mechanism of action of an enzyme involved in cancer. The importance of this work lies in the fact that this enzyme is responsible for the correct functioning of numerous processes within the body and its malfunction is related to a wide spectrum of types of cancer. The information obtained is therefore very valuable since it can be used for the design of more specific and powerful drugs against this enzyme.

The research has been carried out under the direction of Ramón Hurtado-Guerrero, researcher at the ARAID Foundation of the Government of Aragon for talent recruitment, who works at the BIFI of the University of Zaragoza and visiting professor at the University of Copenhagen. Researchers Ana A. García (researcher in training at the University of Zaragoza and DGA scholarship recipient) and Laura Ceballos Laita (PhD from the University of Zaragoza) have worked on this study. Furthermore, in the article published in the journal Nature Communications, "Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase", scientists from CICbiomaGUNE (Sonia Serna, Raik Artschwager, Niels C. Reichardt) and the University of La Rioja (Francisco Corzana).

The scientific journal echoes the advances made by a series of researchers on the molecular basis of how an enzyme called FUT8 transfers a sugar, a fucose in particular, to N-glycans. This modification is called “core fucosylation” and takes place on another sugar linked directly to asparagine residues found in proteins. Asparagine glycosylation in proteins is one of the most abundant post-translational modifications in nature and occurs in hundreds of proteins.

One of the main functions of this enzyme is to modify the activity of antibodies known as "antibody-dependent cellular cytotoxicity" or "ADCC" for short. Therefore, this modification is what regulates the "ADCC" activity of the antibodies. Specifically, it is known that the inhibition of this enzyme generates antibodies with greater "ADCC" activity, which is desirable for their better therapeutic activity.

Due to these mentioned properties of FUT8 both in cancer and in the activity of antibodies, knowledge of the mechanism of this enzyme would open the door to research for the generation of new cancer therapies based on the development of more powerful inhibitors that favor the body's immune response during the fight against this disease.

Through the work published in Nature Communications, it is shown how the key to the FUT8 mechanism lies in the reorganization that takes place in its structure when its substrates are present. The information obtained is therefore very valuable since it can be used for the design of more specific and powerful drugs. Furthermore, this work elucidates the molecular basis of how FUT8 recognizes its ligands and how it transfers a fucose unit to N-glycans.