AI Summary
The article discusses a recent study from Stanford University and the Stanford Synchrotron Radiation Lightsource that has provided new insights into a key enzyme involved in celiac disease, transglutiminase 2 (TG2). Researchers have discovered previously unseen details about the enzyme's structure and how it interacts with gluten and calcium ions to trigger an immune response. This discovery could potentially lead to the development of new drugs to target TG2 and treat celiac disease more effectively.
Celiac disease affects around one in a hundred people worldwide, and those that have the autoimmune disorder have no choice but to stick to a gluten-free diet forever—at the moment, doctors have no other way to treat the illness.
Now, those seeking a treatment could get a boost: A new study from researchers at Stanford University and the Stanford Synchrotron Radiation Lightsource (SSRL) at the U.S. Department of Energy’s SLAC National Accelerator Laboratory has revealed previously unseen details of a key enzyme behind the disease. The study was published in Proceedings of the National Academy of Sciences.
Celiac scientists have known for several years now that the enzyme in question, transglutiminase 2 (TG2), could trigger an immune response in the presence of gluten and calcium ions, leading the body to attack its own intestinal tissues. What has been less clear is exactly how TG2 works and how best to target it with drugs—in part because scientists have only had a limited understanding of the enzyme’s structure. Previous studies have mapped out TG2’s inactive, “closed” state and its active, “open” state, but how it transformed from one to the other or what happens in the interim remained unclear.
To address that problem, Angele Sewa, a graduate student in chemistry and biochemistry in Stanford chemist Chaitan Khosla’s lab and a fellow in the Sarafan ChEM-H Chemistry/Biology Interface Training Program, and Harrison Besser, a student