Multifunctional Activity-Based Protein Profiling of the Developing Lung

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.