3D model reveals enzyme’s attack

U. MELBOURNE (AUS) —Scientists have determined the structure of the enzyme endomannosidase, which clarifies how viruses like HIV and Hepatitis C hijack human enzymes.

The findings open the door to the development of new drugs to combat these deadly viruses that infect more than 180 million people worldwide.

The team studied bacterial endomannosidase as a model for the same human enzyme and determined the three-dimensional structure of the enzyme using state of the art synchrotron technology.


Knowing the structure of the enzyme revealed details on how viruses hijack human enzymes using them to replicate and cause infection, says associate professor Spencer Williams of the Bio21 Institute at the University of Melbourne.

“If we understand how the viruses use our enzymes, we can develop inhibitors that block the pathway they require, opening the door to drug developments,” he says.

“In the past the problem has been that this group of viruses including HIV, Hepatitis C, Dengue Fever, and West Nile virus, are able to bypass the main pathway if inhibited and replicate via a second pathway using this enzyme. Thus for a treatment to be effective, both pathways need to be blocked.

“It was already known how to block the main pathway for these viruses but until now, this endomannosidase bypass pathway has proved a considerable challenge to study.

“Combining international resources and expertise, we were able to determine the endomannosidae structure and this has revealed how we can block the bypass route, stopping the viruses from hijacking human enzymes,” says Williams.

Their findings are published in Proceedings of the National Academy of Sciences.

Davies says that the team hopes that the work will lead beyond viruses and will point the way toward similar treatments for other diseases including cancer.

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