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Multifunctional Activity-Based Protein Profiling of the Developing Lung.

Ethan G Stoddard1, Regan F Volk1, James P Carson2

  • 1Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99352 , United States.

Journal of Proteome Research
|July 5, 2018
PubMed
Summary
This summary is machine-generated.

This study used activity-based probes to map enzyme activity in developing lungs, revealing key enzymes involved in metabolism and protein turnover crucial for infant lung health and development.

Keywords:
activity-based protein profilingchemoproteomicslung development

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Area of Science:

  • Pulmonary Medicine
  • Biochemistry
  • Developmental Biology

Background:

  • Infant lung diseases are a major cause of mortality, often linked to premature birth and environmental exposures.
  • Understanding the molecular mechanisms of lung development is critical for addressing these health issues.

Purpose of the Study:

  • To functionally characterize xenometabolizing cytochrome P450 enzymes, ATP/nucleotide-binding enzymes, and serine hydrolases in the developing lung.
  • To gain insights into cellular metabolism and protein turnover during lung development using activity-based chemoproteomics.

Main Methods:

  • Application of a suite of activity-based probes (ABPs) for chemoproteomic profiling.
  • Detection of enzyme activities including P450s, ATPases, kinases, phosphatases, NAD-/FAD-dependent enzymes, RNA/DNA helicases, and proteases.
  • Correlation of ABP target activities with RNA in situ hybridization analyses.

Main Results:

  • Cytochrome P450 activity was predominantly observed in the postnatal lung.
  • A broad spectrum of ATPases and nucleotide/nucleic acid-binding enzymes involved in cellular metabolism were characterized.
  • Changes in serine hydrolase activities indicated dynamic protein turnover throughout lung development.

Conclusions:

  • Activity-based chemoproteomics provides a powerful functional readout of enzyme activity during lung development.
  • The study identified key enzymes and metabolic pathways active during lung development, offering targets for future research.
  • Findings contribute to a deeper understanding of infant lung health and disease pathogenesis.