Bio

Ming-Daw Tsai received his B. S. degree in chemistry from National Taiwan University, Taipei, in 1972, and his Ph.D. from Purdue University in 1978,working with Heinz. G. Floss. The honors he received include: Alfred P. SloanFellow, 1983-1985; Camille and Henry Dreyfus Teacher-Scholar, 1985-1990;Distinguished Scholar Award of Ohio State University, 1992; Elected Fellow,American Association for the Advancement of Science, 1992. He has served inthe following national panels: NIH Physical Biochemistry Study SectionMember, 1988-92; Co-chair, Gordon Conference on Enzymes, 1993; NIH TrainingGrant Study Section, 1997-present; Board of Consulting Editors, Bioorganic& Medicinal Chemistry, 1998-present; Board of Consulting Editors,Bioorganic & Medicinal Chemistry Letters, 1998-present. In 1995 he becameDirector, Campus Chemical Instrument Center, and in 1995 he also took therole of Program Director, Chemistry/Biology Interface Training Program at OSU.

Research Overview

Protein Structure-Function, NMR, Enzyme Mechanism

My overall research interest lies in the interface between chemistry andbiology. The specific area of interest is the structure-function relationshipof enzymes and proteins. The unique aspect of our research is that we employstate-of-the-art methodology in several areas: organic synthesis, molecularbiology, enzymology, NMR, and other biophysical techniques.(a) Structure-Function Relationship of Tumor Suppressors.We have determined the tertiary structures of tumor suppressors p16 and p15,and have constructed and characterized many mutants. The ultimate goal willbe to use the structure-function information to design new anti-tumor drugs.(b) Structure-Function Relationship of DNA Polymerase-b  and DNA Polymerase X.Although DNA and RNA polymerases have been studied extensively, the basicchemical knowledge in the fidelity is still very primitive. Understanding ofthis important problem at the chemical level can lead to understanding of thedrug resistance of HIV.(c) Structure and Specificity of a New Phosphoprotein Binding Domain FHA.FHA is a newly discovered domain in signal transduction. In collaboration with Dr.Pei, we are using NMR and combinatorial libraries to characterize the structureand ligand specificity of FHA domains from different proteins.(d) Synthesis of Phosphatidylinositol (PI)Analogs and Mechanism of PI-PLC. This project has several significantaspects: PI and related compounds are key compounds in numerous newly discoveredbiological pathways; PI-specific phospholipase C is a key enzyme in thesepathways; and the synthesis of PI analogs is very difficult.(e) Structure-Function Relationship of Phospholipase A2.Phospholipase A2 has unique properties: it has seven disulfide bonds in a small size,14 kDa, and it catalyzes reaction at the surface of membranes or micelles.Detailed structure-function analysis will lead to understanding of theseproblems at the chemical level.

Recent Publications

"A DNA Polymerase with Specificity for Five Base Pairs". Alexander K.Showalter and Ming-Daw Tsai, J. Am. Chem. Soc. 123, 1776-1777 (2001).

"Insight into the Catalytic Mechanism of DNA Polymerase : Structures ofIntermediate Complexes". Joseph W. Arndt, Weimin Gong, Xuejun Zhong,Alexander K. Showalter, Jia Liu, Christopher A. Dunlap, Zheng Lin, ChadPaxson, Ming-Daw Tsai, and Michael K. Chan, Biochemistry 40, 5368 -5375(2001).

"Interfacial Enzymology: The Phospholipase A2 Paradigm". Otto G. Berg,Michael Gelb, Ming-Daw Tsai, and Mahendra K. Jain, Chemical Reviews 101,2613-2653 (2001).

"Structure and Function of the Mutagenic African Swine Fever Virus DNAPolymerase X" by Alexander K. Showalter, In-Ja L. Byeon, Mei-I Su, andMing-Daw Tsai, Nature Structural Biology 8, 942-946 (2001).

"Solution Structures of Two FHA1-Phosphothreonine Peptide Complexes ProvideInsight into the Structural Basis of the Ligand Specificity of FHA1 fromYeast Rad53." Yuan, C., Yongkiettrakul, S., Byeon, I.-J. L., Zhou, S., &Tsai, M.-D., J. Mol. Biol. 314, 573-585 (2001).

"A Reexamination of the Nucleotide Incorporation Fidelity of DNAPolymerases". Alexander K. Showalter and Ming-Daw Tsai, Biochemistry 41,10571-10576 (2002). [New Concepts in Biochemistry]

Li, H., Byeon, I.-J. L., Ju, Y., Tsai, M.-D. "Structure of human Ki67FHA domain and its binding to a phosphoprotein fragment from hNIFK revealunique recognition sites and new views to the structural basis of FHA domainfunctions", J. Mol. Biol. (2003) 335, 371.

"The Catalytic Role of the Aspartate in a Short Strong Hydrogen Bondof Asp274×××His32 Catalytic Dyad in Phosphatidylinositol-specificPhospholipase C Can Be Substituted by a Chloride Ion." Li Zhao, Hua Liao,and Ming-Daw Tsai, J. Biol. Chem. 279, 31995-32000 (2004).

"An Error-Prone Viral DNA Ligase." Brandon Lamarche, Alex Showalter,and Ming-Daw Tsai, Biochemistry 44, 8408-17 (2005).