Ming-Daw Tsai
|
Professor
(joint appointment in the Department of Chemistry)
Phone: 614-292-3080
Fax: 614-292-1685
email: tsai.7@osu.edu
Webpage: Tsai Homepage |
Research Interests:
My overall research interest lies in the interface between chemistry
and biology. The specific area of interest is the structure-function
relationship of enzymes and proteins. The unique aspect of our research
is that we employ state-of-the-art methodology in several areas: organic
synthesis, molecular biology, 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
will be to use the structure-function information to design new anti-tumor
drugs.
(b) Structure-Function Relationship of DNA Polymerase-beta and DNA
Polymerase X. Although DNA and RNA polymerases have been studied extensively,
the basic chemical knowledge in the fidelity is still very primitive.
Understanding of this important problem at the chemical level can lead
to understanding of the drug 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 structure and ligand specificity of FHA domains from different proteins.
(d) Synthesis of Phosphatidylinositol (PI) Analogs and Mechanism of
PI-PLC. This project has several significant aspects: PI and related
compounds are key compounds in numerous newly discovered biological
pathways; PI-specific phospholipase C is a key enzyme in these pathways;
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 these
problems at the chemical level.
Publications
Selected publications from the last 4 years:
Kumar S, Lamarche BJ, Tsai, M-D.. (2007) "Use of Damaged DNA and dNTP Substrates by the Error-Prone DNA Polymerase X from African Swine Fever Virus." Biochemistry [Epub ahead of print]
Li J, Mahajan A, Tsai, M-D.. (2006) "Ankyrin repeat: a unique motif mediating protein -protein interactions." Biochemistry 45(51), 15168-78.
Lamarche BJ, Kumar S, Tsai, M-D.. (2006) "ASFV DNA polymerse X is extremely error- prone under diverse assay conditions and within multiple DNA sequence contexts." Biochemistry 45(49) , 14826 -33.
Ho JY, Huang YT, Wu CJ, Li YS, Tsai, M-D., Li TL. (2006) "Glycopeptide biosynthesis: Dbv21/Orf2 from dbv/tcp gene clusters are N-Ac-Glm teicoplanin pseudoaglycone deacetylases and Orf15 from cep gene cluster is a Glc-1-P thymidyltransferase." J Am Chem Soc 128(42), 13694-5.
Sekar K, Yogavel M, Kanaujia SP, Sharma A, Velmurugan D, Poi MJ, Dauter Z, Tsai, M- D.. (2006) "Suggestive evidence for the involvement of the second calcium and surface loop in interfacial binding: monoclinic and trigonal crystal structures of a quadruple mutant of phospholipase A2." Acta Crystallogr D Biol Crystallogr 62(Pt 7), 717-24.
Sekar K, Gayathri D, Velmurugan D, Jeyakanthan J, Yamane T, Poi MJ, Tsai, M-D.. (2006) "Third calcium ion found in an inhibitor-bound phospholipase A2." Acta Crystallogr D Biol Crystallogr 62 (Pt 4), 392-7.
Sekar K, Yogavel M, Gayathri D, Velmurugan D, Krishna R, Poi MJ, Dauter Z, Dauter M, Tsai, M-D.. (2006) "Atomic resolution structure of the double mutant (K53,56M) of bovine pancreatic phospholipase A2." Acta Crystallograph Sect F Struct Biol Cryst Commun 62(Pt 1), 1-5.
Sekar K, Rajakannan V, Gayathri D, Velmurugan D, Poi MJ, Dauter M, Dauter Z, Tsai, M- D.. (2006) "Atomic resolution (0.97 A) structure of the triple mutant (K53,56,121M) of bovine pancreatic phospholipase A2." Acta Crystallograph Sect F Struct Biol Cryst Commun 61(Pt 1), 3-7.
Lamarche BJ, Tsai, M-D.. (2006) "Contributions of an endonuclease IV homologue to DNA repair in the African swine fever virus." Biochemistry 45(9), 2790-803.
Showalter AK, Lamarche BJ, Bakhtina M, Su MI, Tang KH, Tsai, M-D.. (2006) "Mechanistic comparison of high-fidelity and error-prone DNA polymerases and ligases involved in DNA repair." Chem Rev 106(2), 340-60. Review.
Byeon IJ, Li H, Song H, Gronenborn AM, Tsai
MD. (2005) "Sequential
phosphorylation and multisite interactions characterize specific target
recognition by the FHA domain of Ki67." Nat Struct Mol Biol.
12(11), 987-93.
Mahajan A, Yuan C, Pike BL, Heierhorst J, Chang CF, Tsai
MD. (2005) "FHA
domain-ligand interactions: importance of integrating chemical and biological
approaches." J Am Chem Soc. 127(42), 14572-3.
Li J, Muscarella P, Joo SH, Knobloch TJ, Melvin WS, Weghorst CM, Tsai
MD. (2005) "Dissection of CDK4-binding and transactivation activities
of p34(SEI-1) and comparison between functions of p34(SEI-1) and p16(INK4A)." Biochemistry
44(40), 13246-56.
Apiyo D, Zhao L, Tsai, M-D, Selby TL. (2005) "X-ray structure of
the R69D phosphatidylinositol-specific phospholipase C enzyme: insight
into the role of calcium and surrounding amino acids in active site
geometry and catalysis." Biochemistry 44(30), 9980-9.
Lamarche BJ, Showalter AK, Tsai, M-D. (2005) "An error-prone viral
DNA ligase." Biochemistry 44(23), 8408-17.
Bakhtina M, Lee S, Wang Y, Dunlap C, Lamarche B,Tsai
MD. (2005) "Use
of viscogens, dNTPalphaS, and rhodium(III) as probes in stopped-flow
experiments to obtain new evidence for the mechanism of catalysis by
DNA polymerase beta." Biochemistry 44(13), 5177-87.
Tsai, M-D, Hsieh MS. (2005) "Volume manipulations for simulating
bone and joint surgery." IEEE Trans Inf Technol Biomed. 9(1), 139-49.
Yuan C, Tu S, Gelb MH, Tsai, M-D. (2005) "nusual four-bond secondary
H/D isotope effect supports a short-strong hydrogen bond between phospholipase
A2 and a transition state analogue inhibitor." Biochemistry
44(12), 4748-54.
Hsieh MS, Tsai, M-D, Yeh YD. (2005) "Three-dimensional hip morphology
analysis using CT transverse sections to automate diagnoses and surgery
managements." Comput Biol Med. 35(4), 347-71.
Yuan C, Li J, Mahajan A, Poi MJ, Byeon IJ, Tsai
MD. (2004) "Solution
structure of the human oncogenic protein gankyrin containing seven ankyrin
repeats and analysis of its structure--function relationship." Biochemistry
43(38), 12152-61.
Tsai, M-D, Yeh YD, Hsieh MS, Tsai CH. (2004) "Automatic spinal
disease diagnoses assisted by 3D unaligned transverse CT slices." Comput
Med Imaging Graph. 28(6), 307-19.
O'Maille PE, Tsai, M-D, Greenhagen BT, Chappell J, Noel JP. (2004) "Gene
library synthesis by structure-based combinatorial protein engineering." Methods
Enzymol. 388, 75-91.
Zhao L, Liao H, Tsai, M-D. (2004) "The catalytic role of aspartate
in a short strong hydrogen bond of the Asp274-His32 catalytic dyad in
phosphatidylinositol-specific phospholipase C can be substituted by
a chloride ion." J Biol Chem. 279(31), 31995-2000.
Li J, Melvin WS, Tsai, M-D, Muscarella P. (2004) "The nuclear protein
p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4
in a concentration-dependent manner." Biochemistry 43(14), 4394-9.
Yongkiettrakul S, Byeon IJ, Tsai, M-D. (2004) "The ligand specificity
of yeast Rad53 FHA domains at the +3 position is determined by nonconserved
residues." Biochemistry 43(13), 3862-9.
Pike BL, Yongkiettrakul S, Tsai, M-D, Heierhorst J. (2004) "Mdt1,
a novel Rad53 FHA1 domain-interacting protein, modulates DNA damage
tolerance and G(2)/M cell cycle progression in Saccharomyces cerevisiae." Mol
Cell Biol. 24(7), 2779-88.
Li H, Byeon IJ, Ju Y, Tsai, M-D. (2004) "Structure of human Ki67
FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal
unique recognition sites and new views to the structural basis of FHA
domain functions." J Mol Biol. 335(1), 371-81.
Qin D, Lee H, Yuan C, Ju Y, Tsai, M-D. (2003) " Identification
of potential binding sites for the FHA domain of human Chk2 by in vitro
binding studies." Biochem Biophys Res Commun. 311(4), 803-8.
Li J, Joo SH, Tsai, M-D. (2003) " An NF-kappaB-specific inhibitor,
IkappaBalpha, binds to and inhibits cyclin-dependent kinase 4." Biochemistry
42(46), 13476-83.
Li J, Weghorst CM, Tsutsumi M, Poi MJ, Knobloch TJ, Casto BC, Melvin
WS, Tsai, M-D, Muscarella P. (2003) "Frequent p16INK4A/CDKN2A alterations
in chemically induced Syrian golden hamster pancreatic tumors." Carcinogenesis
25(2), 263-8. .
Sekar K, Vaijayanthi Mala S, Yogavel M, Velmurugan D, Poi MJ, Vishwanath
BS, Gowda TV, Jeyaprakash AA, Tsai, M-D. (003) "Crystal structures
of the free and anisic acid bound triple mutant of phospholipase A2." J
Mol Biol. 333(2), 367-76.
Pike BL, Yongkiettrakul S,Tsai, M-D, Heierhorst J. (2003) "Diverse
but overlapping functions of the two forkhead-associated (FHA) domains
in Rad53 checkpoint kinase activation." J Biol Chem. 278(33), 30421-4.
Poi MJ, Tomaszewski JW, Yuan C, Dunlap CA, Andersen NH, Gelb MH, Tsai
MD. (2003) "A low-barrier hydrogen bond between histidine of secreted
phospholipase A2 and a transition state analog inhibitor." J
Mol Biol. 329(5), 997-1009.
Li J, Li H, Tsai, M-D. (2003) "Direct binding of the N-terminus
of HTLV-1 tax oncoprotein to cyclin-dependent kinase 4 is a dominant
path to stimulate the kinase activity." Biochemistry 42(22), 6921-8.
Yu BZ, Apitz-Castro R,Tsai, M-D, Jain MK. (2003) "Interaction of
monodisperse anionic amphiphiles with the i-face of secreted phospholipase
A2." Biochemistry 42(20), 6293-301.
Li J, Qin D, Knobloch TJ, Tsai, M-D, Weghorst CM, Melvin WS, Muscarella
P. (2003) "Expression and characterization of Syrian golden hamster
p16, a homologue of human tumor suppressor p16 INK4A." Biochem
Biophys Res Commun. 304(2), 241-7.
Mihai, C., Kravchuk, A.V., Tsai, M-D., Bruzik, K.S. (2003) "Application
of Bronsted-Type LFER in the Study of the Phospholipase C Mechanism." J.
Am. Chem. Soc. 125, 3236-42.
Kravchuk, A.V., Zhao, L., Bruzik, K.S., Tsai
MD. (2003) "Engineering
a catalytic metal binding site into a calcium-independent phosphatidylinositol-specific
phospholipase C leads to enhanced stereoselectivity." Biochemistry
42,2422-30.
Zhao, L., Liu, Y., Bruzik, K.S., Tsai, M-D. (2003) "A novel calcium-dependent
bacterial phosphatidylinositol-specific phospholipase C displaying unprecedented
magnitudes of thio effect, inverse thio effect, and stereoselectivity." J.
Am. Chem. Soc. 125, 22-3.
Rajakannan, V., Yogavel, M., Poi, M.J., Jeyaprakash, A.A., Jeyakanthan,
J., Velmurugan, D., Tsai, M-D., Sekar, K. (2002) "Observation
of additional calcium ion in the crystal structure of the triple mutant
K56,120,121M of bovine pancreatic phospholipase A2. J. Mol. Biol. 324, 755-62.
Dunlap, C.A.,Tsai, M-D. (2002) "Use of 2-aminopurine and tryptophan
fluorescence as probes in kinetic analyses of DNA polymerase beta." Biochemistry
41, 11226-35.
O'Maille, P.E., Bakhtina, M.,Tsai, M-D. (2002) "Structure-based
combinatorial protein engineering (SCOPE). J Mol Biol. 321, 677-91.
Showalter, A.K., Tsai, M-D. (2002) "A reexamination of the nucleotide
incorporation fidelity of DNA polymerases. Biochemistry 41, 10571-6.
Tsai, M-D. (2002) "FHA: a signal transduction domain with diverse
specificity and function." Structure (Camb) 10, 887-8.
Li, J., Tsai, M-D. (2002) "Novel insights into the INK4-CDK4/6-Rb
pathway: counter action of gankyrin against INK4 proteins regulates
the CDK4-mediated phosphorylation of Rb." Biochemistry 41, 3977-83.
Byeon, I.J., Yongkiettrakul, S., Tsai, M-D. (2002) "Solution
structure of the yeast Rad53 FHA2 complexed with a phosphothreonine
peptide pTXXL: comparison with the structures of FHA2-pYXL and FHA1-pTXXD
complexes." J. Mol. Biol. 314, 577-88.
