Structural biology, biochemistry, biophysics

1992-1997, Fudan University, Department of Physics, B.A.

1997-1999, City University of New York, City College, Department of Physics, M.A.

1999-2004, State University of New York at Stony Brook, Department of Physiology and Biophysics, phD

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2004-2009, Columbia University, Department of Biological Sciences, postdoc

2009-present, Chinese Academy of Sciences, Institute for Nutritional Sciences, professor

2010-, Structural Biology in Nutritinal Sciences, for first year graduate students

In Peer-reviewd journals:

（1） Crystal Structure of Glycogen Debranching Enzyme and Insights into Its Catalysis and Disease-Causing Mutations, Nature Communications, 2016, Corresponding authour

（2） mRNA quality control at the 5' end, J Zhejiang Univ Sci B, 2014, Corresponding authour

（3） Advances in structural studies of biotin-dependent carboxylases, Chinese Bulletin of Life Sciences, 2013, Corresponding authour

（4） Structure and Function of Allophanate Hydrolase, JBC, 2013, Corresponding authour

（5） Crystal structure of urea carboxylase provides insights into the carboxyltransfer reaction, JBC, 2012, Corresponding authour

（6） Structural and biochemical studies of the 5’-3’ exoribonuclease Xrn1, Nat Struct Mol Biol, 2011, First author
（7） Identification of a quality-control mechanism for mRNA 5’-end capping, Nature, 2010
（8） Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex, Nature, 2010
（9） Cryo-EM Analysis Reveals New Insights into the Mechanism of Action of Pyruvate Carboxylase, Structure, 2010

（10） Structure and function of the 5’-3’ exoribonuclease Rat1 and its activating partner Rai1, Nature, 2009, First author

（11） A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A, Structure, 2009

（12） Real-time fluorescence detection of exoribonucleases, RNA, 2009

（13） A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim, Proc Natl Acad Sci U S A, 2009, First author

（14） Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction, Nat Struct Mol Biol, 2008, First author

（15） Mutational analysis of Escherichia coli MoeA: two functional activities map to the active site cleft, Biochemistry, 2007
（16） structure of 1-deoxy-D-xylulose 5-phosphate synthase, a crucial enzyme for isoprenoids biosynthesis, J Biol Chem, 2007, First author

（17） Crystal structure of human nicotinamide riboside kinase, Structure, 2007, First author

（18） The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites, Cell, 2006
（19） The crystal structure of Cdc42 in complex with collybistin II, a gephyrin-interacting guanine nucleotide exchange factor, J Mol Biol, 2006, First author

（20） Structural insights into sulfite oxidase deficiency, J Biol Chem, 2005

（21） On the relationship between protein stability and folding kinetics: a comparative study of the N-terminal domains of RNase HI, E. coli and Bacillus stearothermophilus L9, J Mol Biol., 2001
（22） The crystal structure of Escherichia coli MoeA and its relationship to the multifunctional protein gephyrin, Structure, 2001,First author

Book chapters:

（1） Ribonucleases (Chapter 7, 5'-3' Exoribonucleases), Springer, 2011-01
（2）Eukaryotic RNases and Their Partners in RNA Degradation and Biogenesis, part A (Chapter 6, Structures of 5'–3' Exoribonucleases), Elsvier, 2012-01
（3） Isoprenoid Synthesis in Plants and Microorganisms: New Concepts and Experimental Approaches (Chapter 2, 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a Crucial Enzyme for Isoprenoids Biosynthesis), Springer, 2013-01, First author

Structure and function of important proteins in metabolism
The cellular metabolism is a very complicated process and involves a large number of proteins, to fully understand the metabolic pathways understanding how the involved proteins function is essential. Our studies aim at revealing the molecular mechanism of proteins that play important roles in metabolism. The techniques  we utilize include X-ray crystallography, biophysical and biochemical assays.  In addition to providing molecular insights into these proteins’ function, our studies will also provide a structural basis for rational drug design.
(1) Lipid and sugar metabolism. Lipid and sugar metabolism is an important part of the cellular energy metabolism; defects of which lead to diseases such as obesity and diabetes, and many proteins involved in lipid and sugar metabolism are important drug targets. The proteins we study in this area including  pyruvate carboxylase (PC) and acetyl-CoA carboxylase (ACC), which catalyzes key  reactions in gluconeogenesis and lipid synthesis; as well as several proteins  involved in the inter-conversion between glucose and glycogen. Both PC and ACC  are members of the biotin-dependent carboxylase family. To fully understand the  general molecular mechanism of enzymes in this family, we also launched studies  of another member in this family, urea amidolyase.
(2) Nucleic acid metabolism. 5’-3’ exoribonucleases (Xrn’s) degrade RNA molecules from their 5’ end, releasing nucleotides. Enzymes in this family, including Xrn1 and Xrn2, are highly conserved among eukaryotes, and have important functions. Xrn1 is  located in the cytoplasm, where it plays a key role in mRNA turnover. Xrn2 is  distributed in the nucleus, and is essential for the transcription termination  process. We have determined crystal structures of Xrn1 and Xrn2, and performed   structure-guided experiments to elucidate the molecular basis of their   exoribonuclease activities. In addition, our studies revealed that Rai1, an  Xrn2 activator, possesses a novel enzymatic activity. Rai1 de-cappes improperly  capped mRNA molecules, allowing them to be degraded. This discovery led to the  identification of a conserved mRNA quality control mechanism in eukaryotes.

phD students graduated

Chen Fan, 2014 

Liting Zhai, 2016

Jing Zhao, 2016

Current students

Yihui Song

Miaomiao Shen

Xin Xu

Xiaofan Li

Jun Yu

Hongwei Zhang

Hang Zhang