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Related Experiment Video

Updated: Jul 17, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
08:17

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

Transition Metal Activation Reframes SAMHD1 Regulation.

Logan A Calderone1, Anthony Gizzi2, Soumika Pinninti1

  • 1Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02453, United States.

ACS Chemical Biology
|July 15, 2026
PubMed
Summary

Iron and other transition metals are crucial for activating SAMHD1, a key enzyme in antiviral defense and nucleotide regulation. The enzyme forms iron-dependent active sites, allowing flexibility to maintain function under varying cellular conditions.

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Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
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Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells

Published on: June 13, 2021

Related Experiment Videos

Last Updated: Jul 17, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
08:17

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
09:43

Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells

Published on: June 13, 2021

Area of Science:

  • Biochemistry
  • Enzymology
  • Molecular Biology

Background:

  • SAMHD1 is a unique human enzyme regulating dNTP hydrolysis, impacting antiviral immunity, nucleotide balance, and disease.
  • Its metal cofactor requirements and roles in catalysis are largely unknown despite extensive study of its other properties.

Purpose of the Study:

  • To elucidate the specific metal cofactors required for SAMHD1 activation and catalysis.
  • To understand the mechanistic roles of these metal ions in enzyme function.

Main Methods:

  • Selective metal enrichment
  • Spectroscopy
  • Biochemical reconstitution
  • Enzyme kinetics

Main Results:

  • SAMHD1 activity is optimally supported by transition metals, particularly iron, which forms dinuclear active sites.
  • Iron initiates bimetallic core assembly, facilitating catalysis, while manganese is a less efficient substitute.
  • The second metal-binding site is flexible, accommodating various ions and enabling mixed-metal active sites that resist oxidative inhibition.
  • Transition metals act as higher-affinity allosteric activators than Mg2+.

Conclusions:

  • This study redefines SAMHD1's metal requirements, highlighting iron's role in organizing active sites.
  • Mixed-metal flexibility allows SAMHD1 to function across diverse cellular metal concentrations and redox states.
  • Metal identity is critical for both catalytic and regulatory functions of SAMHD1.