Structure/function of ATP sulfurylase domain of human 3′-phosphoadenosine 5′-phosphosulfate synthase (hPAPSS)
2024

Study of Human PAPS Synthase and Its ATP Binding Mechanism

publication Evidence: high

Author Information

Author(s): K.V. Venkatachalam, Dhiraj Sinha, Chris Soha, Rudi H. Ettrich

Primary Institution: College of Allopathic Medicine, USA

Hypothesis

The H425NGH428 motif in human PAPS synthase is crucial for ATP binding and enzymatic activity.

Conclusion

Mutating the N426 residue to K426 in human PAPS synthase significantly enhances its catalytic efficiency and ATP binding.

Supporting Evidence

  • The N426K mutant exhibited a 3-4 fold increase in catalytic efficiency compared to the wild type.
  • Mutations of histidine residues H425 and H428 completely abolished ATP sulfurylase activity.
  • In silico studies showed that the N426K mutation resulted in a more favorable ATP binding energy.

Takeaway

Scientists studied a protein that helps make a molecule important for sulfur transfer in the body, and found that changing one part of it made it work better.

Methodology

The study involved site-directed mutagenesis, enzyme assays, and molecular dynamics simulations to analyze the effects of specific mutations on enzyme activity.

Limitations

The study primarily focused on a single mutant and may not represent all possible variations in the enzyme's function.

Digital Object Identifier (DOI)

10.1016/j.bbrep.2024.101892

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