Protein post-translational modifications (PTMs) play a key role in the regulation of diverse cellular physiologies and diseases. Targeting PTM pathways is a hot and promising therapeutic approach in new drug development, such as kinase inhibitors for treatment of cancer and inflammatory diseases.

A novel type of lysine PTM, lysine malonylation (Kmal) has been dicovered by the new established Chemical Proteomics Center(CPC) in Shanghai Institute of Materia Medica, Chinese Academy of Sciences (SIMM) led by Professor ZHAO Yingming at Ben May Department for Cancer Research, University of Chicago, together with the scientists from other research institutions.

This new protein modificationwas initially detected by mass spectrometry, and was comprehensively validated by various chemistry, biochemistry and isotopic labeling experiments. Next, researchers showed that Kmal is a dynamic and evolutionarily conserved modificationin mammalian cells and bacterial cells. Importantly, they demonstrated that Sirt5, a member of the class III lysine deacetylases (HDACs), can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo. This result suggests the possibility of non deacetylation activity of other class III HDACs, especially those without obvious acetylation protein substrates. This study therefore revealed the new function of Sirt5, which provides a promising future for characterization of new biological functions of HDACs and for development of new drugs. The result has been published in the current issue of Molecular and Cellular Proteomics (Mol Cell Proteomics 2011 10: M111.012658.)

In the beginning year of “the twelfth five-year-plan”, SIMM has recruited world-leading scientists as chief scientistsor adjunct faculty members to establish several leading research units, including CPC, International Scientist Working Station of Neuropharmacology and Center for Structures and Function of Drug Targets.These research units dedicate to addressing the key bottlenecks in drug discovery and development, and have made several significant progresses. The senior author of this paper, Professor ZHAO Yingming, was recruited by SIMM as an adjunct faculty member to co-direct CPC in SIMM.