Peptidomics of prolyl endopeptidase in the central nervous system.

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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Nolte WM,Tagore DM,Lane WS,Saghatelian A

doi

10.1021/bi901637c

subject

Has Abstract

pub_date

2009-12-22 00:00:00

pages

11971-81

issue

50

eissn

0006-2960

issn

1520-4995

journal_volume

48

pub_type

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