Western University of Health Sciences Graduate College of Biomedical Sciences Western University of Health Sciences
Graduate College of Biomedical Sciences

Swairjo Lab

Dr. Swairjo standing in front of projection screenThe research in Dr. Swairjo’s lab focuses on elucidating the
function and biosynthesis pathways of key modified nucleosides of transfer-RNA
using a combination of bioinformatic, biochemical and X-ray crystallographic
methods. Our studies of the tRNA modified nucleoside Queuosine led to the
discovery and structure determination of the only nitrile reductase enzyme
known in biology, and its ongoing development by us and others as a
biocatalytic agent for industrial applications, creating an environment
friendly alternative to the hazardous chemical methods currently in use. Our
studies have also resulted in the identification and full characterization of a
new antibacterial drug target that we are currently developing in collaboration
with industry using structure-based drug design methods. Because tRNA
modifications ensure translational fidelity and control in all life forms, they
have been implicated in numerous cell processes in eukaryotes including
mitochondrial dysfunction in human neurodegenerative disease. We are presently
interested in elucidating the role of these modified nucleosides in
mitochondrial function in human neurons and exploring their role in vertebrate
development using a zebrafish model.

 

The crystal structure of the Queuosine biosynthesis nitrile reductase enzyme QueF is an asymmetric tunnel-fold homodecamer of two head-to-head facing pentameric subunits, harboring ten active sites at the interfaces between monomeric subunits, view the video of overall structure and perspective of interfacial catalytic site.

 

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The binding of substrate preQ0 induces closure of the active site, as shown in this video, followed by formation of a thioimide linkage with invariant side chain Cys55. This “induced fit” mechanism of substrate binding may be considered in the re-design of the active site to accept unnatural substrates.

 

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View Dr. Swairjo’s biographical information here