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Aurora magazine

The molecular structure of metastases has been unveiled

The team of Professor Federico Forneris of the University of Pavia has unveiled the molecular structure of the LH3 enzyme. The enzyme regulates the maturation of collagen, the protein that supports cells and tissues. A possible malfunction is related to rare genetic diseases and causes the formation of metastases in the case of a tumor.

The researchers reported for the first time the 3D molecular structure of LH3. To do this they used X-ray crystallography. This has allowed us to obtain many new details on the functioning of the enzyme. In particular, it has given a boost to research on genetic diseases of collagen.

The enzyme LH3 has an atypical molecular structure: two copies of the enzyme work simultaneously, forming an elongated geometry. That's why until yesterday there was little information on LH3. A 3D model was needed to understand its exact functioning. In addition, the researchers found that the enzyme performs more enzymatic activities, which is very rare.

The genetic abnormalities related to LH3 are the basis of serious genetic diseases of bone and connective tissues. Among these are osteogenesis imperfecta, Elhers-Danlos syndrome and Bruck's syndrome. Furthermore, the malfunction of LH3 facilitates the metastasis of different types of cancer. In fact, the enzyme creates collagen pathways around the tumor cells, stimulating their migration.

The Pavia team will use the strategies used for the LH3 study on other enzymes. The goal is to find the genetic and molecular causes that cause the formation of metastases. The hope is to be able to develop drugs that prevent the metastasis of solid tumors.