The research team led by CAS Academicians Zhu Chen and Saijuan Chen made a fundamental discovery of the therapeutic mechanism of As2O3 molecule of the acute promyelocytic leukemia (APL). The discovery demonstrates the promyelocytic leukemia protein (PML, a zinc finger protein) is the direct target of As2O3, which was published in Science on 9 April 2010.

The research has been a long-standing cooperation with the team headed by Prof. Ziyu Wu at the Beijing Synchrotron Radiation Facility (BSRF) of IHEP. By the X-ray absorption spectroscopy (XAS) experiments carried out at 1W1B Beamline of BSRF and the X-ray absorption near edge structure (XANES) quantitative analysis, they discovered that arsenics bound directly to cysteine residues in the two Zn finger domains of the PML protein. Binding takes place at the two zinc sites, and then a ligand moves away from each metal centre forming two three-fold coordinations.

This study shows how the changes that occur in the Zn finger domains of the PML have a great effect on the protein folding and its activity. 

The discovery opens a new route to investigate the mechanism of As2O3 and that of the new drugs for acute promyelocytic leukemia. It is really a multidisciplinary research with a lot of promise for clinical applications. Moreover, arsenic is an ancient drug of the traditional Chinese medicine and with modern techniques; this study may push further development of our traditional medicine.

Prof. Ziyu Wu's team is recognized in the world for BioXAS applications, it is also involved in the development of new theoretical methods.