Crystal structure of the protein OGG1 bound to a key inhibitor. Illustration: Geoffrey Masuyer
“We’ve developed a new drug molecule that inhibits inflammation,” says Professor Thomas Helleday, at the Department of Oncology-Pathology, Karolinska Institutet, Sweden, who led the study.
The enzyme OGG1 triggers inflammation
It was when developing a new molecule for inhibiting the enzyme that repairs oxygen damage to DNA that the researchers found, to their surprise, that it also dampened inflammation. It turned out that the enzyme OGG1, apart from repairing DNA, also triggers inflammation.
The inhibitor blocks the release of inflammatory proteins, such as inflammatory signal proteins. In trials on mice with acute pulmonary disease, the researchers succeeded in dampening the inflammation.
“We use X-ray crystallography and a variety of other methods to study enzymes and their binding to potent inhibitors that we are developing in an interdisciplinary research collaboration. Structural, biophysical and biochemical studies are essential for the understanding of these proteins natural functions and the discovery and development of novel drugs targeting them”, says Pål Stenmark, associate professor at the Department of Biochemistry and Biophysics, Stockholm University, who conducts the research group at Stockholm University who found out how the inhibitor binds and affects OGG1.
The researchers detailed studies of how the inhibitors interacts with OGG1 will now continue.
The researchers hope to develop new treatments
“We hope to together develop new treatments for inflammatory diseases like sepsis, MS, COPD and severe asthma”, says Pål Stenmark.
The article ”Small-molecule inhibitor of OGG1 suppresses pro-inflammatory gene expression and inflammation” is published in the scientific journal Science.
The press release from Karolinska Institutet.
Watch the film “Small molecule inhibitor of OGG1 suppresses pro-inflammatory gene expression and inflammation”.