Characterization of the enzymatic properties of human RNPEPL1/aminopeptidase Z

Abstract

Summary It is now evident that the M1 family of aminopeptidases play important roles in many pathophysiological processes. Among them, the enzymatic properties of Arginyl aminopeptidase-like 1 (RNPEPL1) are characterized only by its truncated form. No peptide substrate has been identified. To characterize the enzymatic properties of RNPEPL1 in more detail, the full-length protein was expressed in E. coli and purified to homogeneity. The full-length RNPEPL1 showed rather restricted substrate specificity and basic amino acid preference toward synthetic substrates, which was different from the previously reported specificity characterized by the truncated form. Searching for peptide substrates, we found that several peptides, such as Met-enkephalin and kallidin, were cleaved. RNPEPL1 cleaved bradykinin to de-[Arg]-bradykinin despite the presence of proline at the P2’-position. The enzyme cleaved Met-enkephalin but not dynorphin A1-17. Similar to aminopeptidase B, the full-length RNPEPL1 showed basic amino acid preference toward both synthetic and peptide substrates. In addition to the unusual cleavage of bradykinin, this enzyme shows chain-length-dependent cleavage of peptide substrates sharing N-terminal amino acid sequence. This is the first study to report the enzymatic properties of the full-length human RNPEPL1 as an aminopeptidase enzyme.

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

“…S8). Increasing donor age was strongly positively correlated to proteins with known (and postulated) roles in aging, cellular senescence, proteolysis and mitochondrial dysfunction: scavenger receptor class B member 2 (SCARB2) (31), arginyl aminopeptidase-like 1 (RNPEPL1) (32), acid ceramidase (ASAH1) (33), and cyclin-dependent kinase inhibitor 2A (CDKN2A) (34) (Fig. 3A).…”

Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma

“…Following this, a predictive model was built utilizing LASSO Cox regression analysis, and nine MMPs-related genes were identified as a prognostic signature, showing an independent correlation with the prediction of HCC prognosis. RNPEPL1, a member of the M1 family of zinc metal peptide enzymes, consists of 12 enzymes in humans and employs Zn 2+ as the central active site [ 18 ]. The individuals in this household participate in various activities, ranging from breaking down peptides and retrieving amino acids in overall cellular proteolysis to controlling physiological signaling sequences by breaking down peptide hormones and processing peptides displayed on class I MHC molecules [ 19 ].…”