Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase.
Prolylcarboxypeptidase (PRCP) is a serine protease that catalyzes the cleavage of C-terminal amino acids linked to proline in peptides. It is ubiquitously expressed and is involved in regulating blood pressure, proliferation, inflammation, angiogenesis, and weight maintenance. To identify the candidate proximal target engagement markers for PRCP inhibition in the central nervous system, we profiled the peptidome of human cerebrospinal fluid to look for PRCP substrates using a MS-based in vitro substrate profiling assay. These experiments identified a single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor-like protein 2.
Zhao
Xuemei
X
Department of Proteomics, Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
Southwick
Katie
K
Cardasis
Helene L
HL
Du
Yi
Y
Lassman
Michael E
ME
Xie
Dan
D
El-Sherbeini
Mohamed
M
Geissler
Wayne M
WM
Pryor
KellyAnn D
KD
Verras
Andreas
A
Garcia-Calvo
Margarita
M
Shen
Dong-Ming
DM
Yates
Nathan A
NA
Pinto
Shirly
S
Hendrickon
Ronald C
RC
D000595:Amino Acid Sequence; D002268:Carboxypeptidases / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity
D010455:Peptides; D002268:Carboxypeptidases; C022448:lysosomal Pro-X carboxypeptidase