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Research Article

The N-terminal SAM domain of the dNTPase SAMHD1 is not required for inhibition by small molecule TH6342

Christopher DirksSciLifeLab, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenView further author information
,
Henri Colyn BwanikaSciLifeLab, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenView further author information
,
Ann-Sofie JemthSciLifeLab, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenView further author information
,
Si Min ZhangSciLifeLab, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenView further author information
&
Sean G. RuddSciLifeLab, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenCorrespondence[email protected]
View further author information
Received 18 Jan 2024, Accepted 25 Feb 2024, Published online: 03 Jun 2024

References

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  • Zhang, S. M.; Paulin, C. B. J.; Shu, H.; Yagüe-Capilla, M.; Michel, M.; Marttila, P.; Ortis, F.; Bwanika, H. C.; Dirks, C.; Venkatram, R. P.; et al. Identification and Evaluation of Small-Molecule Inhibitors against the dNTPase SAMHD1 via a Comprehensive Screening Funnel. iScience 2024, 27, 108907. DOI: 10.1016/j.isci.2024.108907.
  • Yagüe-Capilla, M.; Rudd, S. G. A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1. J. Vis. Exp. 2021. DOI: 10.3791/62503.
  • Morris, E. R.; Caswell, S. J.; Kunzelmann, S.; Arnold, L. H.; Purkiss, A. G.; Kelly, G.; Taylor, I. A. Crystal Structures of SAMHD1 Inhibitor Complexes Reveal the Mechanism of Water-Mediated dNTP Hydrolysis. Nat. Commun. 2020, 11, 3165. DOI: 10.1038/s41467-020-16983-2.
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  • Antequera-Parrilla, P.; Castillo-Acosta, V. M.; Bosch-Navarrete, C.; Ruiz-Pérez, L. M.; González-Pacanowska, D. A Nuclear Orthologue of the dNTP Triphosphohydrolase SAMHD1 Controls dNTP Homeostasis and Genomic Stability in Trypanosoma brucei. Front. Cell. Infect. Microbiol. 2023, 13, 1241305. DOI: 10.3389/fcimb.2023.1241305.
  • Yagüe-Capilla, M.; Castillo-Acosta, V. M.; Bosch-Navarrete, C.; Ruiz-Pérez, L. M.; González-Pacanowska, D. A Mitochondrial Orthologue of the dNTP Triphosphohydrolase SAMHD1 is Essential and Controls Pyrimidine Homeostasis in Trypanosoma brucei. ACS Infect. Dis. 2021, 7, 318–332. DOI: 10.1021/acsinfecdis.0c00551.

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