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.
Department of Proteomics, Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
Xuemei
X
Zhao
Katie
K
Southwick
Helene L
HL
Cardasis
Yi
Y
Du
Michael E
ME
Lassman
Dan
D
Xie
Mohamed
M
El-Sherbeini
Wayne M
WM
Geissler
KellyAnn D
KD
Pryor
Andreas
A
Verras
Margarita
M
Garcia-Calvo
Dong-Ming
DM
Shen
Nathan A
NA
Yates
Shirly
S
Pinto
Ronald C
RC
Hendrickon
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