MAR 13, 2018 12:43 PM PDT

Enzyme's Structure Linked to Heart Disease, Diabetes, Cancer, Parkinson's

WRITTEN BY: Kara Marker

One enzyme’s structure may hold the key to new treatments for a variety of diseases: diabetes, cancer, neurodegenerative disorders, heart disease. Without knowing its structure, researchers have not been successful in developing inhibitor drugs to address the protein’s connection to various conditions through activating the inflammatory pathway. Now, from St. Louis University, scientists have been able to determine the enzyme’s structure.

Photomicrograph of a region of substantia nigra in a Parkinson's patient showing Lewy bodies and Lewy neurites. Credit: Suraj Rajan

"In the past, people have studied this complex enzyme, like a black box, without knowing what is inside," explained Sergey Korolev, PhD. "Now that we have discovered the structure, we can see every atom. This allows us to visualize what is happening with this protein. It is a completely new level of insight."

The enzyme is calcium-independent phospholipase A2β (iPLA2β), which was first discovered more than 20 years ago for its role in type 1 diabetes, then again ten years ago for its role in neurodegenerative disorders. In addition to “iPLA2β,” the enzyme is also referred to as PARK14 in connection to genetic mutations in patients with Parkinson’s disease.

“For example, inherited mutations in this gene were identified in patients with early onset Parkinson's,” Korolev explained.

Korolev and many other scientists are interested in iPLA2β because of its connection to the inflammatory response, a mechanism known to be at the foundation of multiple diseases. Past studies show that iPLA2β cleaves phospholipids in the cell membrane and responds to injury by triggering the immune response.

But without knowing iPLA2β’s molecular structure, researchers couldn’t answer important questions: How is iPLA2β activated during injury? How does it get shut down (deactivating the inflammatory response)?

Korolev and other scientists from St. Louis University were finally able to determine iPLA2β’s molecular structure via x-ray crystallography. What they found was different than what researchers had anticipated.

"Before we had the structure, people didn't have good tools to study this enzyme," Korolev said. “Now, the 3D structure gives us a clear hypothesis for how it is responsible for action in different cellular compartments and tissues.”

"There is a growing amount of genetic work that links iPLA2β to neurodegenerative disease, and physicians and scientists worldwide are now interested in its function," explained MD/PhD student Konstantin Malley. "We are still a long way from treating patients, but I would like them to know that the structure is a large step between genetics and developing targeted therapies for treatment.”

The present study was published in the journal Nature Communications.

Sources: St. Louis University, Diabetes

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
MAR 16, 2020
Drug Discovery & Development
MAR 16, 2020
Critical Interleukin Leads to Drug Discovery
The immune molecule interleukin-2 (IL-2) is a growth factor that stimulates the immune system to produce T-cells. Their ...
MAR 29, 2020
Cell & Molecular Biology
MAR 29, 2020
Learning More About Boosting Immunity in Older Adults
Older adults are more susceptible to infections and don't generate a robust immune response after a vaccination.
APR 01, 2020
Immunology
APR 01, 2020
New Airway-Hugging Immune Cells Discovered in the Lung
  Scientists have discovered a previously unknown subset of immune cells residing in the lung that specifically com ...
APR 21, 2020
Drug Discovery & Development
APR 21, 2020
Researchers Develop COVID-19 Nasal Spray Vaccine
Researchers from the University of Waterloo in Canada are working on a DNA-based vaccine for COVID-19 that can be applie ...
MAY 16, 2020
Neuroscience
MAY 16, 2020
Stem Cell Method (Parkinson's) Could Avoid Transplant Rejection
Researchers at McLean Hospital and Massachusetts General Hospital (MGH) have tested a stem cell treatment method that av ...
JUN 15, 2020
Drug Discovery & Development
JUN 15, 2020
New Antibiotic 'Irresistin' Defeats All Resistant Bacteria
Researchers from Princeton University have identified a compound capable of killing both Gram-positive and Gram-negative ...
Loading Comments...