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J Proteome Res. 2018 Aug 3;17(8):2623-2634. doi: 10.1021/acs.jproteome.8b00086. Epub 2018 Jul 18.

Multifunctional Activity-Based Protein Profiling of the Developing Lung.

Author information

1
Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99352 , United States.
2
Texas Advanced Computing Center , University of Texas at Austin , Austin , Texas 78758 , United States.
3
Department of Pediatrics, Baylor College of Medicine , Jan and Dan Duncan Neurological Research Center at Texas Children's Hospital , Houston , Texas 77030 , United States.
4
The Gene and Linda Voiland School of Chemical Engineering and Bioengineering , Washington State University , Pullman , Washington 99163 , United States.

Abstract

Lung diseases and disorders are a leading cause of death among infants. Many of these diseases and disorders are caused by premature birth and underdeveloped lungs. In addition to developmentally related disorders, the lungs are exposed to a variety of environmental contaminants and xenobiotics upon birth that can cause breathing issues and are progenitors of cancer. In order to gain a deeper understanding of the developing lung, we applied an activity-based chemoproteomics approach for the functional characterization of the xenometabolizing cytochrome P450 enzymes, active ATP and nucleotide binding enzymes, and serine hydrolases using a suite of activity-based probes (ABPs). We detected P450 activity primarily in the postnatal lung; using our ATP-ABP, we characterized a wide range of ATPases and other active nucleotide- and nucleic acid-binding enzymes involved in multiple facets of cellular metabolism throughout development. ATP-ABP targets include kinases, phosphatases, NAD- and FAD-dependent enzymes, RNA/DNA helicases, and others. The serine hydrolase-targeting probe detected changes in the activities of several proteases during the course of lung development, yielding insights into protein turnover at different stages of development. Select activity-based probe targets were then correlated with RNA in situ hybridization analyses of lung tissue sections.

KEYWORDS:

activity-based protein profiling; chemoproteomics; lung development

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