Aizhuo Liu
Research Interests
Dr. Liu's research interests are in the characterization of structure, dynamic, and intermolecular interaction of proteins and protein/nucleic acid complexes through the use of NMR spectroscopy as a major technique to obtain biologically and chemically relevant information on their behaviors. My research includes the development of more efficient solution NMR experimental methods and the use of them to obtain information on three-dimensional atomic structures of biomacromolecules, particularly integral membrane proteins, molecular structure-function relationships, location and time scales of dynamic processes, location and kinetics of ligand interactions, and the effects of solvent conditions on the conformations of the biomacromolecules. I am also interested in the application of new NMR parameters and techniques to the characterization of molecular recognition and protein/small molecule interactions, which is critical information for drug development.
In parallel to running the MSU Biomolecular NMR
Facility, I am conducting the following research projects:
1.) Solution NMR study of integral membrane proteins. Membrane proteins play critical roles in many cellular and physiological processes and represent 70% of the targets for drug development. Despite of their biological significance, structural information on membrane proteins is scarce. The paucity of the structural information on membrane proteins is a major hindrance to the understanding of their functions and the development of new medicines. Dr. Honggao Yan of our Department and I are jointly developing integral membrane protein systems for the solution NMR study. We choose multi-drug transporters as model systems. Multi-drug transporter-mediated extrusion of drugs is one of major problems in chemotherapeutic treatment of cancers and infectious diseases. Knowledge about the structure-function relationships in multi-drug transporters is urgently needed for addressing the problem of multi-drug resistance.
2.) New NMR parameters and techniques for large molecular and supramolecular systems. NMR is an ever-developing technique for the structural and dynamic study of biomacromolecules. MORE
Recent Publications
Liu A, Wang J, Lu Z, Yao L, Li Y, Yan H. (2008) Hydrogen-bond detection, conformation assignment and rotamer correction of side-chain amides in large proteins by NMR spectroscopy through protium/deuterium isotope effects. ChemBioChem 9:2860-2871.
Kron M, Cichanowicz S, Hendrick A, Liu A, Leykam J, Kuhn L. (2008) Using structural analysis to generate parasite-selective monoclonal antibodies. Protein Science 17:938-989.
Liu A, Lu Z, Wang J, Yao L, Li Y, Yan H. (2008) NMR detection of bifurcated hydrogen bonds in large proteins. J Am Chem Soc. 130(8):2428-9. Link to pdf
Liu, A., Yao, L., Li, Y., and Yan, H. (2007) TROSY of side-chain amides in large proteins. J. Magn Reson. 186(2)319-326. Link to pdf
Liu, A., Li, Y., Yao, L., and Yan, H. (2006) Simultaneous NMR assignment of backbone and side chain amides in large proteins with IS-TROSY. J. Biomol. NMR 36, 205-214. Link to pdf
Yao, L., Li, Y. Wu, Y. Liu, A., and Yan, H. (2005) Product release is rate-limiting in the activation of the prodrug 5-Fluorocytosine by yeast cytosine deaminase. Biochemistry 44, 5940-5947. Link to pdf MORE