Summary information and primary citation

PDB-id
8d9j; SNAP-derived features in text and JSON formats; DNAproDB
Class
hydrolase-DNA
Method
X-ray (2.82 Å)
Summary
Samhd1-DNA complex
Reference
Simermeyer TL, Batalis S, Rogers LC, Zalesak OJ, Hollis T (2023): "Protein oxidation increases SAMHD1 binding ssDNA via its regulatory site." Nucleic Acids Res., 51, 7014-7024. doi: 10.1093/nar/gkad447.
Abstract
SAMHD1 dNTP hydrolase activity places it at the crossroad of several important biological pathways, such as viral restriction, cell cycle regulation, and innate immunity. Recently, a dNTPase independent function for SAMHD1 in homologous recombination (HR) of DNA double-strand breaks has been identified. SAMHD1 function and activity is regulated by several post-translational modifications, including protein oxidation. Here, we showed that oxidation of SAMHD1 increases ssDNA binding affinity and occurs in a cell cycle-dependent manner during S phase consistent with a role in HR. We determined the structure of oxidized SAMHD1 in complex with ssDNA. The enzyme binds ssDNA at the regulatory sites at the dimer interface. We propose a mechanism that oxidation of SAMHD1 acts as a functional switch to toggle between dNTPase activity and DNA binding.

Cartoon-block schematics in six views (download the tarball)

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