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.

It was when developing a new molecule for inhibiting the enzyme that repairs oxygen damage to DNA that we, to our surprise, found that it also dampened inflammation. It turned out that the enzyme OGG1, apart from repairing DNA, also triggers inflammation.

Our detailed studies of how the inhibitors bind and affect OGG1 will now continue and we hope to together develop new treatments for inflammatory diseases like sepsis, MS, COPD and severe asthma, says Pål Stenmark


Crystal structure of OGG1 bound to a key inhibitor. Illustration: Geoffrey Masuyer.



Small-molecule inhibitor of OGG1 suppresses pro-inflammatory gene expression and inflammation

Torkild Visnes, Armando Cázares-Körner, Wenjing Hao, Olov Wallner, Geoffrey Masuyer, Olga Loseva, Oliver Mortusewicz, Elisée Wiita, Antonio Sarno, Aleksandr Manoilov, Juan Astorga-Wells, Ann-Sofie Jemth, Lang Pan, Kumar Sanjiv, Stella Karsten, Camilla Gokturk, Maurice Grube, Evert J. Homan, Bishoy M.F. Hanna, Cynthia B. J. Paulin, Therese Pham, Azita Rasti, Ulrika Warpman Berglund, Catharina von Nicolai, Carlos Benitez-Buelga, Tobias Koolmeister, Dag Ivanic, Petar Iliev, Martin Scobie, Hans E. Krokan, Pawel Baranczewski, Per Artursson, Mikael Altun, Annika Jenmalm Jensen, Christina Kalderén, Xueqing Ba, Roman A. Zubarev, Pål Stenmark, Istvan Boldogh, Thomas Helleday.

Science 16 Nov 2018: Vol. 362, Issue 6416, pp. 834-839


Link to film on youtube;