Manal A. Swairjo, Ph.D.
Graduate College of Biomedical Sciences
Phone: 8201 | Join year: 2010
1988 B.Sc. Physics and Mathematics,
1996 Ph.D. Cellular Biophysics Program,
Department of Physics and Chemistry,
Boston University, and Department of Physiology,
Boston University School of Medicine
GCBS 5080 BIOLOGICAL SYSTEMS IN HUMAN DISEASE
My research focuses on tRNA biogenesis processes and their links to human disease. tRNA is an ancient molecule that evolved to be the adapter between amino acids and codons, thus mediating the translation of the genetic code. In its life and times in the cell, a tRNA molecule undergoes extensive processing and handling by diverse enzymes and protein factors. After transcription and removal of introns, the nascent tRNA molecule is trimmed at the 3' and 5' ends and a CCA tri-nucleotide is added to the 3' end. It is also edited, modified and aminoacylated. In eukaryotes, these steps occur in the nucleolus. The fully modified and aminoacylated tRNA is then transported to the cytoplasm through the nuclear pore complex and is "channeled" to the ribosome. Three steps of tRNA biogenesis constitute the core of my ongoing and future research interests: aminoacylation, modification, and nucleocytoplasmic export. Each of these cell-biochemical processes critically depends on specificity of tRNA recognition.
Swairjo M.A., Roberts M.F., Campos M. B., Dedman J.R. & Seaton B.A. (1994). 31P- and 1H NMR studies of the interaction of annexin V with small phosphatidic acid containing unilamellar vesicles. Biochemistry 33: 10944 50.
Swairjo M.A., Concha N.O., Kaetzel M.A., Dedman J.R. & Seaton B.A. (1995). Crystal structures at 1.9 Å resolution of rat annexin V in complex with glycerophosphoserine or glycerophosphoethanolamine: modes of binding to phospholipid polar moieties. Nature Structural Biology 2: 968-74.
Swairjo M.A., Towler E.M., Debouck C. & Abdel-Meguid S.S. (1998). Structural Role of the 30's Loop in Determining the Ligand Specificity of the Human Immunodeficiency Virus protease. Biochemistry 31: 10928-36.
Morales A.J., Swairjo M.A., & Schimmel P. (1999). Structure-Specific tRNA Binding Protein From the Extreme Thermophile Aquifex aeolicus. EMBO J. 18: 3475-83.
Swairjo, M.A.*, Morales A.J., Wang C.-C., Ortiz A.R., & Schimmel P. (2000). Crystal Structure of Trbp111: a Structure-Specific tRNA Binding Protein. EMBO J. 19: 6287-98.
Swairjo M.A., Otero F.J., Yang X.-L., Lovato M.A., et al., Schimmel P. (2004). Alanyl-tRNA synthetase crystal structure and design for acceptor-stem recognition. Mol. Cell. 13: 829-41.
Lovato M.A., Swairjo M.A., Schimmel P. (2004). Positional recognition of a tRNA determinant dependent on a peptide insertion. Mol. Cell. 13: 843-51.
Swairjo M.A. and Schimmel P. (2005). Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase. Proc. Natl. Acad. Sci. USA. 102: 988-93.
Van Lanen S.G., Reader J.S., Swairjo M.A., de Crécy-Lagard V., Lee B., Iwata-Reuyl D. (2005). From cyclohydrolase to oxido-reductase: Discovery of nitrile reductase activity in a common fold. Proc. Natl. Acad. Sci. USA. 102:12, 4264-9.
Swairjo M.A.*, Reddy R.R., Lee B., Van Lanen S.G., Brown S., de Crécy-Lagard V., Iwata-Reuyl D., Schimmel P. (2005). Crystallization and preliminary X-ray characterization of the nitrile reductase QueF - a queuosine biosynthesis enzyme. Acta Crystallogr. F61: 945-8.
Swairjo M.A. and Schimmel P. Structural evidence of the associative mechanism of amino acid activation by a class II synthetase. In preparation.
Swairjo M.A. and Seaton B.A. (1994). Annexin structure and membrane interactions: a molecular perspective. Annual Reviews for Biophysics and Biomolecular Structure. 23: 193 213. Swairjo M.A. (1998) Anti-Factor IX Fab Fragment Crystal Structure and Methods of Use for Peptidomimetic Design. U.S.A. Patent. Invited Talks
"Adaptive evolution in translation." Hauptman-Woodward Institute, Buffalo, N.Y. September 2005.
"Transfer-RNA recognition codes in aminoacylation, modification and transport." Prof. S. Yokoyama's Satellite Workshop at the 2004 International Conference on Aminoacyl-tRNA Synthetases: Ancient Molecules for Future Biology and Medicine. July 2004.
"Inhibitor specificity of HIV proteases: the structural role of residues outside the active site cavity." The National Cancer Institute, Frederick, Maryland . April 1998.
"HIV protease - structural insights into drug resistance." The Scripps Research Institute, La Jolla, CA. January, 1998. "NMR and crystallographic studies of membrane binding by Annexin V." Boston College, Department of Chemistry, Boston, MA. April 1995.