A cDNA for a Trypanosoma brucei cysteine proteinase has been cloned and sequenced. The deduced protein can be divided into four domains, based on homologies with other cysteine proteinases: the pre-, pro- and central regions show considerable homology to the cathepsin L class of mammalian enzymes, whilst the long C-terminal extension distinguishes the trypanosome enzyme from all mammalian cysteine proteinases reported. This 108 amino acid extension, which includes 9 contiguous prolines near the junction with the central domain, appears likely to be processed in part to produce the mature enzyme, and may be involved in targeting the protein within the cell. The trypanosome genome contains more than 20 copies of the cysteine proteinase gene arranged in a long tandem array.
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http://dx.doi.org/10.1016/0014-5793(89)81655-2 | DOI Listing |
Biochemistry
January 2025
Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
In the wake of the pandemic, peptidyl protease inhibitors with Pro-based rigid Leu mimetics at the P position have emerged as potent drug candidates against the SARS-CoV-2 main protease. This success is intuitively attributed to the enhanced hydrophobic interactions and rigidity of Pro-based rigid Leu mimetics in the literature. However, the tertiary amide of proline P derivatives, which hinders the formation of a critical hydrogen bond with the enzyme active site, and the constrained PP conformation, which contradicts the protease preferred β-strand conformation, represent two overlooked disadvantages associated with these inhibitors over traditional inhibitors and, theoretically, should adversely affect their potency.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Yunnan, China.
Currently, an effective treatment for spinal cord injury (SCI) is not available. Due to the irreversible primary injury associated with SCI, the prevention and treatment of secondary injury are very important. In the secondary injury stage, pyroptosis exacerbates the deterioration of the spinal cord injury, and inhibiting pyroptosis is beneficial for recovery from SCI.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Abdominal aortic aneurysm represents a critical pathology of the aorta that currently lacks effective pharmacological interventions. TNF receptor-associated factor 6 (TRAF6) has been established to be involved in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. However, its role in abdominal aortic aneurysm (AAA) remains unclear.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Objective: Breast cancer is the most frequently diagnosed cancer among women, posing significant health risks. This study investigates niosome nanoparticles as a delivery system for Cyclophosphamide (CYC) and Sodium Oxamate (SO) to target apoptotic pathways in MDA-MB-231 breast cancer cells.
Methods: Lipid-based niosomes were prepared using the thin-film hydration method and characterized for size, zeta potential, and Fourier-transform infrared spectroscopy (FTIR) profiles.
Nan Fang Yi Ke Da Xue Xue Bao
January 2025
College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Objectives: To explore the mechanism of Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs).
Methods: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.
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