D9-nitroTyr-MaPylRS

RS/tRNA Foundational Publication Support

Avila-Crump, Savanna, Marcus L Hemshorn, Chloe M Jones, Lea Mbengi, Kyle Meyer, Joshua A Griffis, Subhashis Jana, et al. (2022) 2022. “Generating Efficient Pyrrolysyl-Trna Synthetases For Structurally Diverse Non-Canonical Amino Acids.”. Acs Chemical Biology 17 (12): 3458-3469. doi:10.1021/acschembio.2c00639.

RS/tRNA Pair Development Year
2022

ncAA(s) Incorporated

3-nitro-L-tyrosine

ncAA Structure (png, jpg, jpeg)
3-Nitro-L-tyrosine
ncAA Utility
3-nitroTyr is a natural post-translational modification of proteins typically resulting from protein oxidation by peroxynitrite. It increases in many diseases and with age. Still unknown is if it can be reversed (by a denitrase) and if it has has a purposeful signaling role, or if it is only a modification associated with pathologies. It is known in some cases to contribute to disease pathology, but in most cases it is unknown how much it causes pathology vs. being a consequence of pathology. The ability to site specifically and quantitatively place 3-nitroTyr in positions in proteins that have been seen to occur in association with disease is a key tool to answer questions about its possible roles in normal physiology and disease.

3-Iodo-L-tyrosine

ncAA Structure (png, jpg, jpeg)
3-Iodo-L-tyrosine
ncAA Utility
Aid protein crystal
structure deciphering


RS Organism of Origin
Parent RS
RS Mutations
N166A
V168S
W239R

tRNA Organism of Origin
Parent tRNA
tRNA Anticodon
CUA

RS/tRNA Availability
n/a
Used in what cell line?

RS/tRNA Additional Notes
Generated from a proof-of-principle selection to show that the M alvus library used could be a source of diverse RSs. This and multiple other RSs selected in the study had similar activity with 3NY, with MS confirming full-fidelity incorporation. Incorporation into sfGFP(150) in E coli was at a similar level to both the Mb A7 nitroTyr RS and the Mj A7 nitroTyr RS. The UP50 of the D9 RS was ~40 microM and a permissivity study showed that it and some of the other RSs incorporated 3-chloro, 3-bromo, and 3-iodoTyr at even higher levels than 3-nitroTyr. None of the Ma 3NY RSs were tested for their functionality in mammalian cells or used in an application.