By Li Han
Staff Writer of the Tsinghua News Center
Tsinghua University Professor Wu Jia-Wei published a paper in Nature (June 25, 2009) , entitled “Structural insight into the autoinhibition mechanism of AMP-activated protein kinase”. The group led by Professor Shi Yigong at Tsinghua University published their recent research findings in Science (June 19, 2009), entitled “Structure and mechanism of an amino acid antiporter”.
Professor Wu and her colleagues reported the crystal structures of an unphosphorylated AMPK (AMP-activated protein kinase) fragment that contains a catalytic kinase domain and an autoinhibitory domain (AID), and of a phosphorylated kinase domain. They also carried out extensive in vitro kinetic studies to demonstrate the regulatory mechanism of AMPK activity. The structural and biochemical data have shown how the primary mechanism of AMPK autoinhibition works and suggest a conformational switch model for AMPK activation by AMP. These results may lay a theoretical foundation for the new drug discovery and therapy of type 2 diabetes.
Professor Shi Yigong’s team reported the crystal structure of Adic, an arginine-agmatine antiporter that plays essential role in the acid-resistance system of virulent enteric pathogens. Structural and biochemical analyses revealed the potential ligand-binding sites, and the transport route. Their study suggested a conserved mechanism for the antiporter activity. This is the first crystal structure of the membrane protein in the amino acid/polyamine/organocation (APC) transporter superfamily, a class of transporters that consist of more than 250 members, conserved from bacteria to human being. The reported structure will shed light on the further understanding of APC proteins in prokaryotes and eukaryotes.
