Chemistry & Biochemistry

Curriculum Vitae

• B.Sc., Physics and Mathematics, Kuwait University, 1988
• Ph.D., Cellular Biophysics, Boston University, 1996
• Senior Research Scientist, The Scripps Research Institute, 1998-2005
• Assistant Professor, Western University of Health Sciences, 2010-2015
• Associate Professor, San Diego State University, 2015-2024
• Professor, San Diego State University, 2024-present

Research Interests

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. The coding properties of tRNA do not reside only in its primary sequence. Post-transcriptional nucleoside modification, particularly in the anticodon-stem loop (ASL) region of tRNA, are required for cognate and/or wobble codon recognition and translocation, they enhance aminoacylation properties of tRNA, and prevent ribosomal frameshifting.

Deficiencies in tRNA modifications cause a variety of diseases, e.g. hereditary human mitochondrial disease, and modified nucleosides serve as sensitive human cancer markers. Most significantly, modifications of the anticodon-stem loop have been implicated in viral replication as several retroviruses rely on modifications of host cell tRNA for virulence or to replicate.

In the past five years, my lab focused on elucidating the biosynthesis pathways of three modified tRNA nucleosides: queuosine (Q), archaeosine (G⁺), and threonylcarbamoyl adenosine (t⁶A). Studying these pathways in model microbial systems, in which some of the genes involved are essential, has led to the discovery of several new potential antimicrobial drug targets, as well as new enzymatic mechanisms and unprecedented chemistries such as biological nitrile reduction. Our approach combines X-ray crystallographic, structural bioinformatic and biochemical analyses, complemented by collaborations with geneticists and chemists.

Recent Publications

1. "Crystal structure of the archaeosine synthase QueF-like — Insights into amidino transfer and tRNA recognition by the tunnel fold,"
   Mei, X., Alvarez, J., Bon Ramos, A., Samanta, U., Iwata-Reuyl, D., and Swairjo, M. A.,
   Proteins 85, 103-16 (cover article) (2017). (doi: 10.1002/prot.25202.)
2. "Mechanism and catalytic strategy of the prokaryotic specific GTP cyclohydrolase IB,"
   Paranagama, N., Bonnett, S.A, Alvarez, J., Luthra, A., Stec, B., Gustafson, A., Iwata-Reuyl, D., and Swairjo, M. A.,
   Biochemical J. 474, 1017-1039 (cover article) (2017). (doi: 10.1042/BCJ20161025.)
3. "Protection of the queuosine biosynthesis enzyme QueF from irreversible oxidation by a conserved intramolecular disulfide,"
   Mohammad, A., Bon Ramos, A., Lee, B., Cohen, S., Kiani, M. K., Iwata-Reuyl, D., Stec, B., and Swairjo, M. A.,
   Biomolecules 7, 30 (2017). (doi: 10.3390/biom7010030.)
4. "Structure and mechanism of a bacterial t⁶A biosynthesis system,"
   Amit Luthra, William Swinehart, Susan Bayooz, Phuc Phan, Boguslaw Stec, Dirk Iwata-Reuyl, and Manal A. Swairjo,
   Nucleic Acids Research 46, 1395-1411 (2018). (doi: 10.1093/nar/gkx1300.)
5. "Conformational communication mediates the reset step in t⁶A biosynthesis,"
   Amit Luthra, Naduni Paranagama, William Swinehart, Susan Bayooz, Phuc Phan, Vanessa Quach, Jamie M. Schiffer, Boguslaw Stec, Dirk Iwata-Reuyl, and Manal A. Swairjo,
   Nucleic Acids Research , gkz439 (2019). (doi: 10.1093/nar/gkz439/5494771.)
6. "Inhibitor potency varies widely among tumor-relevant human isocitrate dehydrogenase 1 mutants,"
   Diego Avellaneda Matteo, Grace A. Wells, Lucas A. Luna, Adam J. Grunseth, Olga Zagnitko, David A. Scott, An Hoang, Amit Luthra, Manal A. Swairjo, Jamie M. Schiffer, Christal D. Sohl,
   Biochem. J. 475, 3221-3238 (2018). (doi: 10.1042/BCJ20180424.)
7. "Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens,"
   Yifeng Yuan, Rémi Zallot, Tyler L. Grove, Daniel J. Payan, Isabelle Martin-Verstraete, Sara Šepić, Seetharamsingh Balamkundu, Ramesh Neelakandan, Vinod K. Gadi, Chuan-Fa Liu, Manal A. Swairjo, Peter C. Dedon, Steven C. Almo, John A. Gerlt, and Valérie de Crécy-Lagard,
   PNAS 116, 19126-19135 (2019). (doi: 10.1073/pnas.1909604116.)
8. "Structure-based design of guanosine analogue inhibitors targeting GTP cyclohydrolase IB towards a new class of antibiotics,"
   Samaan G. N., Paranagama N., Haque A., Hecht D. A., Swairjo M. A., Purse B. W.,
   Bioorg. Med. Chem. Lett. 30, 126818 (2019). (doi: 10.1016/j.bmcl.2019.126818.)
9. "Specificity in the Biosynthesis of the Universal tRNA Nucleoside N6-Threonylcarbamoyl Adenosine (t6A) - TsaD is the Gatekeeper,"
   Swinehart W. E., Deutsch C. W., Sarachan K. L., Luthra A., Bacusmo J. M., de Crécy-Lagard V. E., Swairjo M. A., Agris P. F., and Iwata-Reuyl D.,
   RNA (in press) (2020). (doi:rna.075747.120.)
10. "Detection of preQ₀ deazaguanine modifications in bacteriophage CAjan DNA using Nanopore sequencing reveals same hypermodification at two distinct DNA motifs,"
    Kot W., Olsen N. S., Nielsen T. K., Hutinet G., de Crécy-Lagard V., Cui L., Dedon P. C., Carstens A. B., Moineau S., Swairjo M. A., Hansen L. H.,
    Nucleic Acids Research , gkaa735 (2020). (doi: 10.1093/nar/gkaa735.)
11. "Predicting the capsid architecture of phages from metagenomic data,"
    Diana Y. Lee, Caitlin Bartels, Katelyn McNair, Robert A. Edwards, Manal A. Swairjo, Antoni Luque,
    Computational and Structural Biotechnology Journal 20, 721-732 (2022). (doi: 10.1016/j.csbj.2021.12.032.)
12. "Structural basis of Qng1-mediated salvage of the micronutrient queuine from queuosine-5'-monophosphate as the biological substrate,"
    Hung S.H., Elliott G.I., Ramkumar T.R., Burtnyak L., McGrenaghan C.J., Alkuzweny S., Quaiyum S., Iwata-Reuyl D., Pan X., Green B.D., Kelly V.P., de Crécy-Lagard .V, Swairjo M.A.*,
    Nucleic Acids Res. 51, 935-951 (2023). (doi: 10.1093/nar/gkac1231.)
13. "7-Deazaguanines in DNA: functional and structural elucidation of a DNA modification system,"
    Samanthi Gedara, Evan Wood, Andrew Gustafson, Cui Liang, Shr-Hau Hung, Joshua Savage, Phuc Phan, Amit Luthra, Valérie de Crécy-Lagard, Peter Dedon, Manal A. Swairjo* and Dirk Iwata-Reuyl,
    Nucleic Acids Research , gkad141 (2023). (doi:10.1093/nar/gkad141.)