Education Ph.D Case Western Reserve University 1974 B.S. University of Michigan 1970 Research Fellow National Institutes of Health 1978-1983 Professional Experience Associate Professor Baylor University 1983-Present Visiting Scientist National Institutes of Health 1988, 1989, 1991

Biochemistry

In biochemistry, the field of enzymology has broad applications: from fundamental questions of enzyme mechanism to the utilization of enzymes in numerous areas of biotechnology and the development of therapeutic agents by the pharmaceutical industry. Research in my laboratory is directed toward the investigation of enzymes involved in the formation and degradation of e-(g-glutamyl)lysine and g-glutamylpolyamine crosslinks in proteins with emphasis on mechanism of enzyme action, the purification and properties of individual enzymes, and the design and synthesis of enzyme inhibitors and substrates.

Transglutaminases are a widely distributed group of enzymes that catalyze covalent crosslinking of proteins and peptides through e-(g-glutamyl)lysine linkages and through di-g-glutamylpolyamine bonds. The catalytic power of these enzymes is required for the stabilization of fibrin clots during hemostasis, in wound healing, for crosslinking of membrane proteins during skin development, and in fertilization.

The role of transglutaminases in cell regulation including cell proliferation, and macrophage activation is currently being investigated. Specific inhibitors of Factor XIIIa, the transglutaminase of the blood clotting cascade, will be applied to the investigation of the physiological role of this enzyme and may prove useful as therapeutic agents in preventing thrombosis. We are using a model system to evaluate target compounds that are analogs of peptide substrates as enzyme inhibitors. We have developed a fluorometric HPLC assay for transglutaminase using a small synthetic compound and a fluorescent amine as substrates. We have extended this assay to evaluate additional peptide substrates including Substance P and endorphin.

The laboratory is equipped with a peptide synthesizer an HPLC, and an amino acid analyzer. NMR, FT-IR, high-resolution mass spectrometry and x-ray crystallography are also tools used to determine the structure of synthetic compounds. In studies designed to elucidate the catabolism of e-(g-glutamyl)lysine crosslinks and other biological products of the action of the enzyme transglutaminase, we discovered an enzyme, g-glutamylamine cyclotransferase (g-GACT) that can act on e-(g-glutamyl)lysine, g-glutamyl derivatives of putrescine, histamine, spermidine, spermine and amines to give 5-oxo-proline and free amine. To determine if this enzyme functions in the catabolism of crosslinked proteins, we are currently characterizing g-GACT with respect to its basis for specificity.

AlAsiri, S., Basit, S., Wood-Trageser, M.A., Yatsenko, S.A., Jeffries, E.P., Surti, U., Ketterer, D.M., Afzal, S., Ramzan, R., Faiyaz-Ul Haque, M., Jiang, H, Trakselis, M.A., Rajkovic, A. (2015) Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. J. Clin. Invest., 125 (1), 754-62. link

Wood-Trageser, M.A., Gurbuz, F., Yatsenko, S.A., Jeffries, E.P., Kotan, L.D., Surti, U., Ketterer, D.M., Matic, J., Chipkin, J., Jiang, H, Trakselis, M.A., Topaloglu, A.K., Rajkovic, A. (2014) Exome sequencing identifies MCM9 mutations in ovarian failure, short stature and chromosomal instability. Am. J. Hum. Genetics, 95 (6), 754-762. link

Nucleic Acid Polymerases, Murakami, K. and Trakselis, M.A. (Eds.), Nucleic Acids and Molecular Biology Vol. 30, Berlin, Germany, Springer. 2014. link

Trakselis, M.A. and Murakami, K. Introduction to Nucleic Acid Polymerases: Families, Themes, and Mechanisms, (Chapter 1), Nucleic Acid Polymerases, Murakami, K. and Trakselis, M.A. (Eds.), Nucleic Acids and Molecular Biology Vol. 30, Berlin, Germany, Springer. 2014. link

Trakselis, M.A. and Bauer, R.J. Archaeal DNA Polymerases: Enzymatic Abilities, Coordination, and Unique Properties, (Chapter 6), Nucleic Acid Polymerases, Murakami, K. and Trakselis, M.A. (Eds.), Nucleic Acids and Molecular Biology Vol. 30, Berlin, Germany, Springer. 2014. link

Bauer, R.J., Wolff, I.D., Zuo, X., Lin, H-K., Trakselis, M.A. (2013) Assembly and Distributive Action of an Archaeal DNA Polymerase Holoenzyme. Special Issue of J. Mol. Biol. entitled “DNA replication & Genomic instability – Replicon Theory”, 425 (230), 4820-36. link

Mohan S., Das, D., Bauer R.J., Heroux A., Zalewski, J.K., Heber, S., Dosunmu-Oqunbi, A.M., Trakselis, M.A., Hildebrand J.D., and VanDemark A.P (2013) Structure of a Highly Conserved Domain of Rock1 Required for Shroom-mediated Regulation of Cell Morphology. PLOS One, 8(12), e81075. link

van Dongen, S.F.M., Clerx, J., Nørgaard, K., Bloemberg. T.G., Cornelissen, J.J.L.M., Trakselis, M.A., Nelson, S.W., Benkovic, S.J., Rowan, A.E., Nolte, R.J.M. A Clamp-Shaped Bio-Hybrid Catalyst for DNA Oxidation. Nature Chem., 5(11), 946-51. link

Jeffries, E.P., Denq, W.I., Bartko, J.C., and Trakselis, M.A. (2013) Identification, Quantification, and Evolutionary Analysis of a Novel Isoform of MCM9, Gene, 519, 41-49. link

Bauer, R.J., Graham, B.W., and Trakselis, M.A. (2013) Novel Interaction of the Bacterial-like DnaG Primase with the MCM Helicase in Archaea, J. Mol. Biol., 8(26), 1259-1273. link

Trakselis, M.A. and Graham, B.W. (2012) Biochemisty: Molecular Hurdles Cleared with Ease, Nature, 492, 195-197. link

Lin, H-K., Chase, S.F., Laue, T.M., Jen-Jacobsen, L., and Trakselis, M.A. (2012) Differential Temperature Dependent Multimeric Assemblies of Replication and Repair Polymerases on DNA Increase Processivity. Biochemistry,51, 7367-7382. link

Mohan, S., Rizaldy, R., Das D., Bauer R.J., Heroux A., Trakselis, M.A., Hildebrand J.D., Vandemark, A.P. (2012) Structure of the shroom domain 2 reveals a three-segmented coiled-coil required for dimerization, rock binding, and apical constriction, Mol. Biol. Cell, 23, 2131-2142. link

Bauer, R.J., Begley M.T., and Trakselis, M.A. (2012) Kinetics and fidelity of polymerization by DNA polymerase III from Sulfolobus solfataricus, Biochemistry, 51, 1996-2007. link

Zuo, Z., Lin, H-K, and Trakselis, M.A. (2011) Strand annealing and terminal transferase activities of a B-family DNA Polymerase, Biochemistry, 50, 5379-5370. link

Graham, B.W., Schauer, G.D., Leuba, S.H. and Trakselis, M.A. (2011) Steric Exclusion and Wrapping of the Excluded DNA Strand Occurs Along Discrete External Binding Paths During MCM Helicase Unwinding, NAR, 39, 6585. link

Zuo, Z., Rodgers, C., Mikheikin, A.L., and Trakselis, M.A. (2010) Characterization of a functional DnaG-type primase in Archaea: Implications for a dual primase system, J. Mol. Biol., 397, 664-676. link

Mikheikin A.L., Lin, H-K, Mehta, P., Jen-Jacobson, L., and Trakselis, M.A. (2009) The DNA replication polymerase from Sulfolobus solfataricus forms a multimer when bound to DNA, NAR, 37, 7194-205. link

Rothenberg, E., Trakselis, M.A., Bell, S.D., and Ha, T. (2007) MCM Forked substrate specificity involves dynamic interaction with the 5′-tail. JBC, 282, 34229-34. link

McGeoch, A.T., Trakselis, M.A., Laskey, R.A., and Bell, S.D. (2005) Organization of the Archaeal MCM Complex on DNA and Implications for a Helicase Mechanism. Nat Struc. Mol. Biol., 12, 756-762. (Cover) link