Wenshe . Liu
Assistant Professor of Chemistry
Ph.D., University of California-Davis
Contact
Information:
Department of Chemistry
Texas A&M University
College Station, TX 77842
Phone:
(979) 845-1746
Fax:
wliu@chem.tamu.edu
Selenium is essential to human life and occurs in selenoproteins as selenocysteine, the 21st amino acid. The selenium atom endows selenocysteine with unique biophysical and biochemical features including a low pKa, unique NMR signal and a high nucleophility and bestows selenoproteins with distinctive catalytic properties such as peroxide reduction and deionization. In human beings, at least 25 specific selenoproteins have been identified, most of which are crucial for human health. However, functional study of these selenoproteins has been hampered by the challenge of selenoproteins’ recombinant expression. In order to overcome this obstacle, one of the major projects in my group is to employ molecular biology, chemical biology and cellular engineering to devise reliable ways of getting E.coli, yeast, or mammalian cells to integrate selenocysteine site-specifically into their proteins. This targeted insertion of selenocysteine into recombinant proteins could make it possible to study any of naturally occurring selenoproteins such as glutathione peroxidases, thyroid hormone deiodinases and thioredoxin reductases. Furthermore, because selenocysteine has unique biophysical and biochemical features, site-specific incorporation of selenocysteine into proteins could facilitate studies of protein folding and provide a chemical handler for introducing a wide range of biophysical probes and post-translational mimics to proteins.
In biology, signal transduction is any process by which a cell transduces one kind of signal into another, most often involving ordered sequences of biochemical reactions inside the cell. This sequential signal transduction is usually carried out by enzymes and mediated by protein-protein interactions to pass on the message. This process plays a fundamental role in many biological processes and dysfunctions of signaling molecules are related to many diseases (e.g. cancer). Protein-protein interactions are of central importance for virtually every signal transduction pathway in a living cell. Information about these interactions will improve our understanding of diseases and can provide the basis for new therapeutic approaches. A multitude of methods have been developed to detect protein-protein interactions in living cells; however, many protein-protein interactions in signal transductions are temporary and rapid and usually escape from the common used detection methods. For this reason, another major project in my group is to design novel protein-protein interaction detection methods to introduce different crosslinking reagents into signaling molecules to permanently link them to their temporary binding proteins that can then be purified and identified by mass spectrometry.
Xie, J.; Liu, W. & Schultz, P.G. A genetic encoded bidentate, metal ion binding amino acid. Angew. Chem. Int. Ed., in press
Tippmann, E.M.†; Liu, W.†; Summerer, D.; Mack, A.V. & Schultz, P.G. A genetic encoded diazirine photocrosslinker in Escherichia coli. ChemBioChem, in press (†authors with equal contributions)
Liu, C.C.; Braustad, E.; Liu, W.* & Schultz, P.G.* Crystal structure of a biosynthetic sulfo-hirudin complexed with thrombin. J. Am. Chem. Soc., 129, 10648-10649, (2007) (*corresponding authors)
Liu, W.; Alfonta, L.; Mack, A.V. & Schultz, P.G. Structural basis for the recognition of p-benzoyl-L-phenylalanyl by evolved aminoacyl-tRNA synthetases. Angew. Chem. Int. Ed. 46, 6073-6075 (2007)
Liu, W.; Brock, A.; Chen, S.; Chen, S. & Schultz P.G. The genetic incorporation of unnatural amino acids into proteins in mammalian cells. Nat. Methods. 4, 239-44 (2007)
Fogle, E.J.; Liu, W.; Keller, J. & Toney, M.D. Role of Q52 in the decarboxylation and transamination of dialkylglycine decarboxylase. Biochemistry 44, 16392-404 (2005)
Liu, W.; Peterson, P.E.; Langston, J.A.; Jin, X.; Zhou, X.; Fisher, A.J. & Toney, M.D. Kinetic and crystallographic analysis of active site mutants of Escherichia coli γ-aminobutyrate aminotransferase. Biochemistry 44, 2982-92 (2005)
Liu, W.; Peterson, P.E.; Carter, R.J.; Zhou, X.; Langston, J.A.; Fisher, A.J. & Toney, M.D. Crystal structures of unbound and aminooxyacetate-bound Escherichia coli γ-aminobutyrate aminotransferase. Biochemistry 43, 10896-905 (2004)
Liu, W. & Toney, M.D. Kinetic and thermodynamic analysis of the interaction of cations with dialkylglycine decarboxylase. Biochemistry 43, 4998-5010 (2004)
Liu, W.; Rogers, C.J.; Fisher, A.J. & Toney, M.D. Aminophosphonate inhibitors of dialkylglycine decarboxylase: structural basis for slow binding inhibition. Biochemistry 41, 12320-28 (2002)
