更新于：2024-11-01

XPNPEP1

更新于：2024-11-01

基本信息

别名

Aminoacylproline aminopeptidase、Cytosolic aminopeptidase P、sAmp

+ [11]

简介

Metalloaminopeptidase that catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro (PubMed:11106490, PubMed:35165443, PubMed:18515364). Contributes to the degradation of bradykinin (PubMed:11106490).

关联

项与 XPNPEP1 相关的药物

CQ31

靶点

PEPD x XPNPEP1

作用机制

PEPD抑制剂 [+1]

在研机构

Memorial Sloan Kettering Cancer Center

原研机构

Memorial Sloan Kettering Cancer Center

在研适应症

炎症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CQ80

靶点

PEPD x XPNPEP1

作用机制

PEPD抑制剂 [+1]

在研机构

Memorial Sloan Kettering Cancer Center

原研机构

Memorial Sloan Kettering Cancer Center

在研适应症-

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 XPNPEP1 相关的临床结果

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100 项与 XPNPEP1 相关的转化医学

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0 项与 XPNPEP1 相关的专利（医药）

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180

项与 XPNPEP1 相关的文献（医药）

2024-04-03·Journal of Agricultural and Food Chemistry

Characterization, Semirational Design for pH Robustness, and the Application in Bioactive Peptide Production of a X-Prolyl Dipeptidyl Aminopeptidase from Lactococcus lactis MY-3

Article

作者: Yu, Junjie ; Gu, Shengdi ; Zhang, Daihui ; Zhao, Li ; Du, Lei ; Xie, Jingli

PepXLcMY-3, an X-prolyl dipeptidyl aminopeptidase derived from Lactobacillus lactis MY-3, was screened and recombinantly expressed in Escherichia coli. The enzyme could exhibit about 40% activity within the pH range of 6.0-10. To further improve the pH robustness, site E396 located in the active pocket was discovered through alanine scanning. The mutant E396I displayed both developed activity and k_cat/K_m. The optimal pH of E396I shifted from 6.0 to 10 compared to WT, with the relative activity within the pH range of 6.0-10 significantly increased. The site K648 was then proposed by semirational design. The activity of mutant E396I/K648D reached 4.03 U/mg. The optimal pH was restored to 6.0, and the pH stability was further improved. E396I/K648D could totally hydrolyze β-casomorphin 7 within 30 min. The hydrolysate showed 64.5% inhibition on angiotensin I converting enzyme, which was more efficient than those produced by E396I and WT, 23.2 and 44.7%, respectively.

2024-02-01·Aging Cell

Proteome‐wide profiling reveals dysregulated molecular features and accelerated aging in osteoporosis: A 9.8‐year prospective study

Article

作者: Yang, Zhen-Xiao ; Yue, Liang ; Chen, Danyu ; Xu, Jinjian ; Hu, Wei ; Cai, Xue ; Chen, Yu-Ming ; Xu, Ying ; Guo, Tiannan ; Zhuo, Laibao ; Fu, Yuanqing ; Wang, Jia-Ting ; Xue, Zhangzhi ; Yan, Yan ; Miao, Zelei ; Zheng, Ju-Sheng

AbstractThe role of circulatory proteomics in osteoporosis is unclear. Proteome‐wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography–tandem mass spectrometry (LC–MS/MS) at baseline, and the 2nd, and 3rd follow‐ups (7704 person‐tests) in the prospective Chinese cohorts with 9.8 follow‐up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual‐energy X‐ray absorptiometry (DXA) at follow‐ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)‐related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed‐effects model (LMM). Meta‐analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta‐analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD‐year increase in KDM‐Proage was associated with higher risk of LS‐OP (hazard ratio [HR], 1.25; 95% CI, 1.14–1.36, p = 4.96 × 10−06), and FN‐OP (HR, 1.13; 95% CI, 1.02–1.23, p = 9.71 × 10−03). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging.

2023-09-01·Journal of Cellular Physiology

The aminopeptidase LAP3 suppression accelerates myogenic differentiation via the AKT‐TFE3 pathway in C2C12 myoblasts

Article

作者: Nagatomi, Ryoichi ; Takada, Hiroaki ; Murayama, Kazutaka ; Kano, Yutaka ; Naoki, Suzuki ; Tabuchi, Ayaka ; Kitajima, Yasuo ; Osana, Shion

AbstractSkeletal muscle maintenance depends largely on muscle stem cells (satellite cells) that supply myoblasts required for muscle regeneration and growth. The ubiquitin–proteasome system is the major intracellular protein degradation pathway. We previously reported that proteasome dysfunction in skeletal muscle significantly impairs muscle growth and development. Furthermore, the inhibition of aminopeptidase, a proteolytic enzyme that removes amino acids from the termini of peptides derived from proteasomal proteolysis, impairs the proliferation and differentiation ability of C2C12 myoblasts. However, no evidence has been reported on the role of aminopeptidases with different substrate specificities on myogenesis. In this study, therefore, we investigated whether the knockdown of aminopeptidases in differentiating C2C12 myoblasts affects myogenesis. The knockdown of the X‐prolyl aminopeptidase 1, aspartyl aminopeptidase, leucyl‐cystinyl aminopeptidase, methionyl aminopeptidase 1, methionyl aminopeptidase 2, puromycine‐sensitive aminopeptidase, and arginyl aminopeptidase like 1 gene in C2C12 myoblasts resulted in defective myogenic differentiation. Surprisingly, the knockdown of leucine aminopeptidase 3 (LAP3) in C2C12 myoblasts promoted myogenic differentiation. We also found that suppression of LAP3 expression in C2C12 myoblasts resulted in the inhibition of proteasomal proteolysis, decreased intracellular branched‐chain amino acid levels, and enhanced mTORC2‐mediated AKT phosphorylation (S473). Furthermore, phosphorylated AKT induced the translocation of TFE3 from the nucleus to the cytoplasm, promoting myogenic differentiation through increased expression of myogenin. Overall, our study highlights the association of aminopeptidases with myogenic differentiation.