Team reveals world-first 3-D image of a protein involved in cancer spread

November 2, 2015, Griffith University
Professor Mark von Itzstein, Director of Griffith University's Institute for Glycomics Credit: Griffith University

Griffith University's Institute for Glycomics has made scientific history by determining the first three-dimensional image of a protein linked to the spread of cancer.

The world-first image is revealed today (Nov. 2) in the prestigious journal Nature Chemical Biology in a paper titled 'Functional and structural characterization of a heparanase', by the Institute's Director, Professor Mark von Itzstein, and his team.

Professor von Itzstein said the 3-D image shows the architecture and intimate atomic-level detail of a bacterial heparanase, an that degrades a sugar molecule known as .

He said the functionally identical human enzyme is over-expressed in cancers and is known to be associated with angiogenesis—a process through which new form from pre-existing vessels—inflammation and increased metastatic potential, making it a promising drug target.

Until now researchers from across the world have only be able to make a 'best guess' from computational studies of what the 3-D structure of this enzyme looked like.

"We have successfully crystallized and determined the structure of the enzyme by X-ray crystallography, making it the first reported heparanase X-ray crystal structure in the world," Professor von Itzstein said.

"This tells us exactly where substrates bind in the catalytic domain and we explored this region by mutating certain amino acids that kill the activity so that we can understand how the enzyme works.

"The bacterial and human heparanase share identical substrate preference and catalytic machinery, thus enabling our heparanase structure to be used in the drug discovery process in targeting the human enzyme."

Professor von Itzstein added that structural and functional analysis of this enzyme provided an exciting opportunity for structure-guided anti-cancer and anti-angiogenesis inhibitor discovery, particularly mechanism-based inhibitor discovery.

"This research has been 10 years in the making and we will now turn our focus to developing a novel anti-cancer drug," he said.

The Institute for Glycomics is the only one of its kind in Australia and only one of six in the world.

"Our research is a brave new frontier and we are making great advances towards the discovery of new drugs, vaccines and diagnostics for significant diseases, including various cancers," Professor von Itzstein said.

"We have grown from a handful of researchers to more than 180 of the best from across the world."

Explore further: Team combats human parainfluenza virus

More information: Functional and structural characterization of a heparanase, Nature Chemical Biology, DOI: 10.1038/nchembio.1956

Related Stories

Breakthrough in battle against leukemia

March 13, 2013

Scientists at Griffith University's Institute for Glycomics and The Saban Research Institute of Children's Hospital Los Angeles have discovered a critical weakness in leukaemic cells, which may pave the way to new treatments.

New inhibitor has potential as cancer drug

October 22, 2007

Laboratory experiments have previously shown that cancer cells overproduce an enzyme, heparanase, which splits the body’s own polysaccharide heparan sulfate into shorter fragments. The amount of enzyme is related to the ...

Unveiling how rotavirus causes infection

January 6, 2015

Researchers from Griffith University's Institute for Glycomics and the University of Melbourne have significantly advanced understanding of a virus that kills up to half a million children each year.

Scientists make big discovery in antibiotics research

July 21, 2015

Scientists seeking to develop the next generation of antibiotics may have found a crucial clue within the human body: a protein that distinguishes between our cells and those of invading microbes, according to a study led ...

Recommended for you

A protein that self-replicates

February 22, 2018

ETH scientists have been able to prove that a protein structure widespread in nature – the amyloid – is theoretically capable of multiplying itself. This makes it a potential predecessor to molecules that are regarded ...

Newly designed molecule binds nitrogen

February 22, 2018

Wheat, millet and maize all need nitrogen to grow. Fertilisers therefore contain large amounts of nitrogenous compounds, which are usually synthesised by converting nitrogen to ammonia in the industrial Haber-Bosch process, ...

Squid skin could be the solution to camouflage material

February 22, 2018

Cephalopods—which include octopuses, squid, and cuttlefish—are masters of disguise. They can camouflage to precisely match their surroundings in a matter of seconds, and no scientist has quite been able to replicate the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.