8D9J

SAMHD1-DNA complex

Summary for 8D9J

• Entry DOI: 10.2210/pdb8d9j/pdb
• Descriptor: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, DNA (5'-D(*CP*AP*AP*TP*G)-3'), FE (III) ION, ... (5 entities in total)
• Functional Keywords: dna complex, catalytic domain, dntp hydrolysis, antiviral protein, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 295621.50

Authors

Hollis, T.J.,Batalis, S.M. (deposition date: 2022-06-10, release date: 2023-07-05, Last modification date: 2024-10-30)

Primary citation

Simermeyer, T.L.,Batalis, S.,Rogers, L.C.,Zalesak, O.J.,Hollis, T.
Protein oxidation increases SAMHD1 binding ssDNA via its regulatory site.
Nucleic Acids Res., 51:7014-7024, 2023

PubMed 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.

PubMed: 37246644
DOI: 10.1093/nar/gkad447

Experimental method

X-RAY DIFFRACTION (2.82 Å)