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

Dirks C, Bwanika HC, Jemth AS, Zhang SM, Rudd SG

Nucleosides Nucleotides Nucleic Acids 43 (8) 831-836 [2024-06-03; online 2024-06-03]

Sterile alpha motif and histidine-aspartic acid domain containing protein-1 (SAMHD1) is a deoxynucleoside triphosphate (dNTP) hydrolase that controls dNTP pools and detoxifies cancer cells of chemotherapy metabolites. TH6342 is a recently reported small molecule inhibitor of SAMHD1 that interacts with the protein in vitro and non-competitively prevents dimerisation, a prerequisite for catalysis. The binding site of TH6342 on SAMHD1 is currently unknown. In the present study we demonstrate that the N-terminal SAM domain of SAMHD1 is not required for inhibition by TH6342.

PubMed 38830230

DOI 10.1080/15257770.2024.2325439

Crossref 10.1080/15257770.2024.2325439