Work

Peptidomics of Prolyl Endopeptidase in the Central Nervous System

Year: 2009

Type: article

Abstract: Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest because of its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep-regulated peptides in the central nervous system (CNS) of mice by measuring changes in the peptidome as a function of Prep activity. This approach was validated by the identification of known Prep substrates, such as the neuropeptide substance P and thymosin-beta4, the precursor to the bioactive peptide Ac-SDKP. In addition to these known substrates, we also discovered that Prep regulates many additional peptides, including additional bioactive peptides and proline rich peptides (PRPs). Biochemical experiments confirmed that some of these Prep-regulated peptides are indeed substrates of the enzyme. Moreover, these experiments also supported the known preference of Prep for shorter peptides while revealing a previously unknown cleavage site specificity of Prep when processing certain multi-proline-containing peptides, including PRPs. The discovery of Prep-regulated peptides implicates Prep in new biological pathways and provides insights into the biochemistry of this enzyme.

Source: Biochemistry

DOI: 10.1021/bi901637c

Authors: Whitney M. Nolte, Debarati M. Tagore, William S. Lane, Alan Saghatelian

Institutions: Harvard University, Center for Systems Biology

Language: English

Topic: Peptidase Inhibition and Analysis

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: Discovery metabolite profiling of the prolyl peptidases, G439425583, G4633533656, Joint Program in Molecules,Cells and Organisms