Shape-shifter’s structure regulates activity

Tamjeed Saleh, PhD, Paolo Rossi and Charalampos Kalodimos, PhD

From left: Tamjeed Saleh, PhD, Paolo Rossi and Charalampos Kalodimos, PhD

St. Jude structural biologists have figured out how the structure of an enzyme called Abl regulates its activity.

Abl switches itself on and off by altering its shape. Knowing how that works is important because a mutant form of the enzyme (Bcr-Abl) is over-activated in chronic myeloid leukemia (CML) and other cancers.

Abl controls growth in white blood cells. The enzyme’s over-activation spurs mutated cells to multiply, causing leukemia.

Although clinicians have successfully treated CML with drugs that switch off the enzyme, Abl often mutates to become drug resistant. The St. Jude study reveals new details about such drug-resistant mutations. The findings also offer a path to possible treatments to overcome that resistance.

The research, led by Charalampos Kalodimos, PhD, St. Jude Structural Biology chair, appeared in Nature Structural & Molecular Biology.

Read the news release.

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