UTA scientists map function of enzymes to provide keys for developing new drugs

Reviewed by Alina Shrourou, B.Sc. (Editor)Aug 30 2018

UTA biochemists are mapping the function of specific enzymes which may facilitate development of new drugs to fight bacterial infection, cancer and potentially neurodegenerative diseases like autism, Down syndrome, Parkinson's disease and Alzheimer's.

"Sulfur is the one of most abundant elements in the body but little is known about the enzymes involved in its metabolism," said Brad Pierce, UTA associate professor of biochemistry and project lead.

"Autistic, Alzheimer and Down syndrome patients all demonstrate abnormal sulfur metabolism. If we can work out how human sulfur-oxidizing enzymes function, or more crucially, how their behavior changes in bacteria or in specific diseases, this information could be used for the rational design of drugs targeted for these diseases. Currently, no such technology exists."

Pierce recently received a $429,033 National Institutes of Health grant to continue his work retro-engineering the sulfur oxidation process and mapping out of the chemical mechanism of three key enzymes - cysteine dioxygenase, cysteamine dioxygenase, and 3-mercaptopropionic acid dioxygenase - to provide the necessary framework to develop effective therapies and drugs for different disease states.

"By comparing the behavior of these enzymes in humans to bacteria we can also open up opportunities to stamp out "superbugs" by providing an alternate means to disrupt bacterial metabolism without adversely affecting the patient," Pierce said. "This is particularly important as we are now seeing widespread drug-resistant bacterial strains."

Pierce's team uses rapid-mix, freeze-quench techniques to 'trap' and monitor the progress of chemical reactions at millisecond intervals. Analysis of these results provides a step-by-step picture of how these enzymes function in both mammals and bacteria.

UTA chair of chemistry and biochemistry Fred MacDonnell congratulated Pierce on his new grant.

"Dr. Pierce's group looks at fundamental life processes outside the traditional sphere of biochemistry and employs very modern techniques to investigate enzyme function and regulation," said Fred MacDonnell, UTA chair of chemistry and biochemistry.

"By providing the fundamental scientific background needed to develop therapies for critical conditions, his lab could make a real impact on the development of new medical solutions."