Post-proline endopeptidase (PPE, EC 3.4.21.26) was purified 3,450 times from human lung. PPE was routinely assayed with the artificial substrate, carbobenzoxy-glycyl-L-prolyl-p-nitroanilide (Z-Gly-Pro-pNA). The pH optimum was 7.4, and the Mr was 77,000. Thiol blocking agents were strongly inhibitory but serine blocking agents were not inhibitory. No metal ions were required for activity, but heavy metal ions such as Hg2+, Cu2+, Cd2+, and Zn2+ completely inactivated the enzyme. Both dithiothreitol (DTT) and ethylenediaminetetraacetic acid (EDTA) were required to stabilize PPE activity. Michaelis constant values for Z-Gly-Pro-pNA and carbobenzoxy-glycyl-L-prolyl-2-naphthylamide were 0.36 and 0.10 mmol/l, respectively. PPE cleaved vasoactive peptides including bradykinin (BK) and des-(Arg9)-BK (Pro3-Gly4 and Pro7-Phe8 bonds), angiotensins I and II (Pro7-Phe8 bond), substance P (Pro4-Gln5 bond), and oxytocin (Pro7-Leu8 bond). Each of these peptides inhibited PPE-catalyzed hydrolysis of Z-Gly-Pro-pNA competitively. BK had the lowest Ki value (2.35 mumol/l) and oxytocin had the highest Ki value (84.0 mumol/l). PPE was not inhibited by captopril, a potent inhibitor of angiotensin converting enzyme, which also cleaves the Pro7-Phe8 bond of BK.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000469289 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Design, Synthesis and Anti-Inflammatory Evaluation of 3-Substituted 5-Amidobenzoate Derivatives as Novel P2Y Receptor Antagonists via Structure-Guided Molecular Hybridization.
J Med Chem
January 2025
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.
View Article and Find Full Text PDFType 3 deiodinase activation mediated by the Shh/Gli1 axis promotes sepsis-induced metabolic dysregulation in skeletal muscles.
Burns Trauma
January 2025
Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, Nanjing, Jiangsu 210008, China.
Background: Non-thyroidal illness syndrome is commonly observed in critically ill patients, characterized by the inactivation of systemic thyroid hormones (TH), which aggravates metabolic dysfunction. Recent evidence indicates that enhanced TH inactivation is mediated by the reactivation of type 3 deiodinase (Dio3) at the tissue level, culminating in a perturbed local metabolic equilibrium. This study assessed whether targeted inhibition of Dio3 can maintain tissue metabolic homeostasis under septic conditions and explored the mechanism behind Dio3 reactivation.
View Article and Find Full Text PDFDosimetric Planning Comparison for Left Ventricle Avoidance in Non-small Cell Lung Cancer Radiotherapy.
Cureus
December 2024
Physics and Engineering, London Regional Cancer Program, London, CAN.
Introduction: Radiation may unintentionally injure myocardial tissue, potentially leading to radiation-induced cardiac disease (RICD), with the net benefit of non-small cell lung cancer (NSCLC) radiotherapy (RT) due to the proximity of the lung and heart. RTOG-0617 showed a greater reduction in overall survival (OS) comparing higher doses to standard radiation doses in NSCLC RT. VHeart has been reported as an OS predictor in the first- and fifth-year follow-ups.
View Article and Find Full Text PDFSynthesis, cytotoxicity, apoptosis-inducing activity and molecular docking studies of novel isatin-podophyllotoxin hybrids.
RSC Adv
January 2025
Institute of Chemistry, Vietnam Academy of Science and Technology (VAST) 18 Hoang Quoc Viet, Cau Giay Hanoi Vietnam
Podophyllotoxin, along with its numerous derivatives and related compounds, is well known for its broad-spectrum pharmacological activity, especially for anticancer potential. In this study, several isatin-podophyllotoxin hybrid compounds were successfully synthesized with good yields through microwave-prompted three-component reactions of 2-amino-1,4-naphthoquinone, various substituted isatins, and tetronic acid. Their cytotoxicity was assessed against four types of human cancer cell lines, HepG2 (hepatoma carcinoma), MCF7 (breast cancer), A549 (non-small lung cancer), and KB (epidermoid carcinoma), alongside nontumorigenic HEK-293 human embryonic kidney cells.
View Article and Find Full Text PDFA cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine.
Res Pract Thromb Haemost
January 2025
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Background: Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.
Objectives: To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!