Characterization of the N7 RNA cap methyltransferase from Trichomonas vaginalis and inhibitor discovery
- 1IOCB
Abstract
RNA cap formation is essential for eukaryotic gene expression, yet the enzymes responsible for cap methylation remain poorly characterized in many eukaryotic parasites, including Trichomonas vaginalis. Here, we functionally and structurally characterized the RNA guanine-N7 methyltransferases (MTases) from T. vaginalis, TvRNMT1 and TvRNMT2. We determined the crystal structure of TvRNMT1 in complex with S-adenosylhomocysteine (SAH) at 1.6 A resolution and additional structures with the inhibitors sinefungin and OBO101, defining the architecture and ligand-recognition properties of its active site. Screening of SAH analogues identified several inhibitors with submicromolar to low-micromolar activity against both homologues. Molecular docking and modelling of capped RNA binding further delineated the inhibitor- and RNA-binding regions of TvRNMT1 and identified residues that may contribute to cap recognition. These results define the molecular basis of ligand recognition by T. vaginalis RNA cap MTases and establish a structural framework for targeting parasite RNA capping.
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BibTeX
@misc{benysek2026characterization,
title = {{Characterization of the N7 RNA cap methyltransferase from Trichomonas vaginalis and inhibitor discovery}},
author = {J. Benysek and D. Chalupska and M. Stefek and O. Bobileva and T. Otava and M. Dejmek and B. Rozycki and R. Nencka and E. Boura},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750033},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750033v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Characterization of the N7 RNA cap methyltransferase from Trichomonas vaginalis and inhibitor discovery
AU - J. Benysek
AU - D. Chalupska
AU - M. Stefek
AU - O. Bobileva
AU - T. Otava
AU - M. Dejmek
AU - B. Rozycki
AU - R. Nencka
AU - E. Boura
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750033
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750033v1
AB - RNA cap formation is essential for eukaryotic gene expression, yet the enzymes responsible for cap methylation remain poorly characterized in many eukaryotic parasites, including Trichomonas vaginalis. Here, we functionally and structurally characterized the RNA guanine-N7 methyltransferases (MTases) from T. vaginalis, TvRNMT1 and TvRNMT2. We determined the crystal structure of TvRNMT1 in complex with S-adenosylhomocysteine (SAH) at 1.6 A resolution and additional structures with the inhibitors sinefungin and OBO101, defining the architecture and ligand-recognition properties of its active site. Screening of SAH analogues identified several inhibitors with submicromolar to low-micromolar activity against both homologues. Molecular docking and modelling of capped RNA binding further delineated the inhibitor- and RNA-binding regions of TvRNMT1 and identified residues that may contribute to cap recognition. These results define the molecular basis of ligand recognition by T. vaginalis RNA cap MTases and establish a structural framework for targeting parasite RNA capping.
ER -