AI Summary
The article discusses a study that delves into the atomic-level structural models of enzymes involved in clearing nucleic acids to prevent autoimmune and inflammatory diseases. The research focuses on PLD3 and PLD4 enzymes, exploring their structures and molecular details to potentially design therapies for diseases like lupus, rheumatoid arthritis, and Alzheimer's disease. Enzymes play a crucial role in maintaining cellular environments, and understanding their structures could provide insights for developing treatments. The study used X-ray crystallography to create atomic-scale models of the enzymes in various states, observing changes in their shapes during the catalytic reaction.
When nucleic acids like DNA or RNA build up in a cell’s cytoplasm, it sets off an alarm call for the immune system. Enzymes usually clear these nucleic acids before they cause an issue, but when these enzymes don’t work and the immune system gets called in, it can lead to autoimmune and inflammatory diseases.
In a new study published on March 26, 2024 in the journal Structure, Scripps Research scientists present the previously undescribed structure of two of these nucleic acid-degrading enzymes-;PLD3 and PLD4. Understanding these enzymes’ structures and molecular details is an important step toward designing therapies for the various diseases that arise when they malfunction, which include lupus erythematosus, rheumatoid arthritis and Alzheimer’s disease.
These enzymes are important for cleaning up the cellular environment, and they also set the threshold for what is considered an infection or not. I’m hoping someday we may be able to help patients based on this information.”
David Nemazee, PhD, senior author, professor in the Department of Immunology and Microbiology at Scripps Research
Enzymes are proteins that speed up chemical reactions by binding and reacting to specific molecules called substrates. In the case of PLD3 and PLD4, the substrate is a strand of RNA or DNA, which the enzymes break down nucleotide by nucleotide.
The team used X-ray crystallography to build atomic-scale models of the PLD3 and PLD4 in multiple states or situations, allowing them to examine how their shapes changed over the course of the catalytic reaction. This included