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Identification of first-in-class enzyme involved in childbirth and muscle diseases

New Stanford research has identified an enzyme that plays a critical role in uterine contractions as well as in other muscle tissues.

What started as research pertaining to viral infections has unexpectedly led to the discovery of a first-in-class enzyme in mammals that modifies muscle proteins to help them grow and remain strong.

According to a Stanford News article, the discovery of the enzyme, called SETD3, solves a 50-year-old mystery of how and why a specific modification (often observed after exercise) to a protein in muscles occurs.

The study was published in Nature.

The protein, SETD3, adds a molecule called a methyl group to a certain location on a protein — actin — found in muscle fibers. That process is what gives the newly-identified enzyme its classification as a histidine methyltransferase, the first of its kind to be discovered in animals; it was only previously documented in yeast.

The addition of methyl "accelerates the formation of new actin filaments in cells, priming them for greater strength when next flexed," the article explains.

The study points to the enzyme's likely role as a key factor in a variety of processes, such as the muscle contractions of the uterus during childbirth, as well as a range of human muscle tissue diseases, because actin is an essential protein for a diverse set of cellular functions, says Stanford biologist Or Gozani, PhD, a co-senior author.

Gozani reflects on the study's findings:

Overall, there are a lot of ‘firsts’ in the study. We discovered a first-in-class enzyme, the first function for histidine methylation in animals or plants, solved a 50-year-old mystery by determining the function of actin histidine methylation and raised the curtain on a new field that may impact human health.

Photo of a cross-section of smooth muscle tissue by Berkshire

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