With that fundamental knowledge in hand, Gelb now has turned his attention to understanding the function and regulation of human PLA2 enzymes in the eicosanoid pathway. Together with Gerard Lambeau of IPMC-CNRS in Valbonne, France, he has identified and characterized a number of new and unusual PLA2 proteins, including a catalytically inactive variant that may act as a receptor ligand instead of an enzyme. He’s also taken an interest in the cytosolic phospholipase enzymes and how they interact with the secreted enzymes in various processes.
Some of these novel proteins could hold therapeutic promise, including one (sPLA2-X) that participates in the synthesis of asthma-inducing leukotrienes and another (sPLA2-IIa) that is involved in rheumatoid arthritis.
“We’ve got some exciting results, though it hasn’t been quite enough yet for pharmaceutical companies to take notice,” says Gelb. “I guess they’re being a little cautious these days.”
It’s no big deal, though; with nine different phospholipase A2 groups in humans, along with several variants in each group, Gelb has plenty of work to keep him busy until that day comes along.
JBC highlight: Valentin, E., Ghomashchi, F., Gelb, M. H., Lazdunski, M., and Lambeau, G. (200) Novel human secreted phospholipase A2 with homology to the group III bee venom enzyme. J. Biol. Chem. 275, 7492 – 7496.
Professor, Chemistry and Structural Biology Division
Institute of Biomedicine, University of Queensland, Australia
While the United States may not be a major hub for venom studies, it probably comes as no surprise that Australia is an important center for venom research.
As Richard Lewis notes, it’s logical given the abundant source material. “Australia has some of the deadliest spiders, snakes, fish and jellyfish in the world,” he says. “I think the only venomous animal for which we’re not at the top of the list is our scorpions.”
Understanding this deadly fauna has been of great interest to Australian researchers for years, and the country has been a pioneer in areas like developing antivenoms and using compression bandages to treat snakebites.