Protein and Peptide Letters - Volume 32, Issue 2, 2025
Volume 32, Issue 2, 2025
-
-
Structural and Functional Insights into UDGs
Authors: Shreya Roy, Md Khabeer Azhar and Vibha GuptaEndogenous or exogenous DNA damage needs to be repaired, therefore, cells in all the three domains have repair pathways to maintain the integrity of their genetic material. Uracil DNA glycosylases (UDGs), also known as UNGs (uracil-DNA N-glycosylases), are part of the base-excision repair (BER) pathway. These enzymes specifically remove uracil from DNA molecules by cleaving the glycosidic bond between the uracil base and the deoxyribose sugar. UDGs can be broadly classified into six families, and each of them share conserved motifs that are critical for substrate recognition and catalysis. Recently, an unconventional UDG known as UDGX has been identified from the species Mycobacterium smegmatis, which is different from other UDG members in forming an irreversible and extremely stable complex with DNA that is resistant to even harsh denaturants such as SDS, NaOH, and heat. This suicide inactivation mechanism prevents uracil excision and might play a protective role in maintaining genome integrity, as bacterial survival under hypoxic conditions is reduced due to the overexpression of MsmUDGX. Additionally, due to the importance of UDGs, the number of structures has been resolved . Moreover , high-resolution 3D structures of apo MsmUDGX, as well as uracil and DNA-bound forms, are available in PDB. This review aims to provide insights into the specific structural-functional aspects of each UDG family member for theragnostic applications.
-
-
-
Amphibian-Derived Antimicrobial Peptides: Essential Components of Innate Immunity and Potential Leads for New Antibiotic Development
More LessLike other vertebrates, amphibians possess innate and adaptive immune systems. At the center of the adaptive immune system is the Major Histocompatibility Complex. The important molecules of innate immunity are antimicrobial peptides (AMPs). These peptides are secreted by granular glands in the skin and protect the animal against microorganisms entering its body through the skin. AMPs offer an effective and rapid defense against pathogenic microorganisms and have cationic and amphiphilic structures. These peptides are small gene-encoded molecules of 8-50 amino acid residues synthesized by ribosomes. These small molecules typically exhibit activity against bacteria, viruses, fungi, and even cancer cells. It is known that today's amphibian AMPs originated from a common precursor gene 150 million years ago and that the origin of these peptides is preprodermaseptins. Today, antibiotic resistance has occurred due to the incorrect use of antibiotics. Traditional antibiotics are becoming increasingly inadequate. AMPs are considered promising candidates for the development of new-generation antibiotics. Therefore, new antibiotic discoveries are needed. AMPs are suitable molecules for new-generation antibiotics that are both fast and have different killing mechanisms. One of the biggest problems in the clinical applications of AMPs is their poor stability. AMPs generally have limited tropical applications because they are sensitive to protease degradation. Coating these peptides with nanomaterials to make them more stable can solve this problem.
-
-
-
Pro-fertility and Antioxidant Potentials of Vigna unguiculata (Cowpea) Protein Isolate and Essential Oil: An In vivo and In silico Studies
More LessIntroductionVigna unguiculata (Cowpea), a legume rich in phytochemicals, has been traditionally used to improve fertility and treat various ailments. This study used in-silico and in- vivo methods to evaluate the effects of cowpea protein isolate and essential oil on reproductive hormonal and antioxidant indices.
MethodsForty (40) female rats were divided into eight groups (n=5). After 14 days of treatment, hormone levels (progesterone, prolactin, testosterone and estradiol) and antioxidant activities (superoxide dismutase (SOD), catalase (CAT) were assessed using biochemical kits and standard procedures. Molecular docking studies were performed using PyRx and Biovia Discovery Studio 2021. The ligands generated through gas chromatography-mass spectroscopy (GCMS) analysis of cowpea oil and the target proteins (SOD and CAT) were from downloaded PubChem and RCSB Protein Data Bank, respectively.
ResultsThe results of this study showed that cowpea essential oil and protein isolate significantly (p<0.05) reduced plasma CAT and SOD activities while increasing their activities in the ovary and liver tissues compared to the infertile untreated group. Consistent administration of either cowpea oil or protein isolate was observed to positively regulate the hormonal indices in the infertile treated groups. Phthalic acid, 2-cyclohexyl ethyl isobutyl ester demonstrated a strong binding affinity and binding constant with SOD and CAT, which suggests that the ligands from cowpea essential oil may have antioxidant and pro-fertility properties that could be developed to treat fertility-related issues.
ConclusionBased on the results of this study, it can be concluded that V. unguiculata has antioxidant property, and can promote fertility, possibly through its rich embedded phytochemicals, which substantiates its traditional claim.
-
-
-
ZP3 Expression in Pancreatic Adenocarcinoma: Its Implications for the Prognosis and Therapy
Authors: Guizhen Lyu and Dongbing LiBackgroundThe role of Zona pellucida glycoprotein 3 (ZP3) is unclear in pancreatic adenocarcinoma (PAAD).
ObjectiveThis study aimed to explore the role of ZP3 in PAAD.
MethodsA comparative analysis of ZP3 gene expression was performed to discern differences between various types of cancer and PAAD, leveraging data sourced from The Cancer Genome Atlas (TCGA). This study aimed to assess the role of ZP3 as a potential diagnostic marker for PAAD. The relationship between ZP3 levels and clinical characteristics, as well as patient outcomes, was scrutinized. Additionally, genomic enrichment analysis was carried out to uncover the underlying regulatory mechanisms associated with ZP3. The study further delved into the association of ZP3 with immune system interactions, checkpoint gene expression, Tumor Mutational Burden (TMB), microsatellite instability (MSI), and tumor stemness index (mRNAsi). The aberrant expression patterns of ZP3 in PAAD cell cultures were confirmed through the application of quantitative reverse transcription PCR (qRT-PCR) techniques.
ResultsZP3 exhibited aberrant expression in both pan-cancer and PAAD. A significant correlation was observed between increased levels of ZP3 expression in PAAD patients and histologic grade (p = 0.026). Elevated ZP3 expression in PAAD was found to be significantly associated with poorer overall survival (p = 0.003), progression-free survival (p = 0.012), and disease-specific survival (p = 0.002). In PAAD, the level of ZP3 gene expression was statistically significant (p < 0.001) and recognized as a key determinant of patient prognosis. ZP3 exhibited associations with various biological pathways, including primary immunodeficiency, oxidative phosphorylation, and other pathways. ZP3 expression demonstrated correlations with immune infiltration, immune checkpoint genes, TMB, MSI, and mRNAsi in PAAD. Moreover, a pronounced negative correlation was detected between ZP3 expression levels and the therapeutic effectiveness of various medications, including selumetinib, bleomycin, FH535, docetaxel, and tanespimycin, within the context of PAAD. Elevated levels of ZP3 were consistently observed in cell line models of PAAD.
ConclusionZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients with PAAD.
-
-
-
Clay-Polymer Nanocomposites Mediated Inhibition of Protein Aggregation: Possible Role in the Prevention of Proteinopathies
Authors: Romana Parveen, Sher Ali and Sadaf FatimaBackgroundThe transformation of proteins from their native conformation into highly ordered fibrillar structures due to their misfolding and aggregation under particular conditions are described as beta-sheet enriched amyloid fibrils. The accumulation of these fibrils in different body parts is the major cause of several neurological and non-neurological conditions (proteinopathies).
ObjectivesTo prevent these proteinopathies, inhibition of protein aggregation is considered a promising strategy. Therefore, in this study, we synthesized montmorillonite (MMT) based poly-orthophenylenediamine (PoPD) nanocomposites (NCs) and characterized their size and morphology due to their remarkable biological properties. Further, the effect of these nanocomposites on inhibition of fibril formation was assessed.
MethodsThese nanocomposites were evaluated for their anti-amyloidogenic potential on two model proteins of amyloidopathies, i.e., human lysozyme and human serum albumin (HL & HSA), by using several biophysical methods, such as Thioflavin T (ThT) and 1-anilino-8-naphthalene sulfonate (ANS) fluorescence, congo red dye binding assay (CR). Secondary structural content was evaluated by Circular dichroism (CD) spectroscopy.
ResultsResults demonstrated that synthesized nanocomposites significantly inhibited fibril formation in dose-dependent manner that corresponds to their ability to arrest fibrillation. It is suggested that they may adsorb proteins to protect them against aggregation when they are subjected to aggregating conditions.
ConclusionThis study offers an opportunity to understand the mechanism of inhibition of fibril formation by nanocomposites, showing that they inhibit amyloid formation and amyloid diseases. Thus, the study concludes that these nanocomposites are promising candidates as therapeutic molecules for proteinopathies and are envisaged to enrich the area of personalized medicine, augmenting the human healthcare system.
-
-
-
Molecular Interactions of the Antimicrobial Peptide Tritrpticin with Mixed Nanoaggregates: A Fluorescence Spectroscopy Study
IntroductionTritrpticin (TRP3) is a peptide belonging to the cathelicidin family and has a broad spectrum of antimicrobial activity. However, this class of biomolecules can be easily degraded in the body, making it necessary to use an efficient transport system. The ability to form stable nanostructures from the interaction of glycyrrhizin saponin with the pluronic polymer F127 was demonstrated, forming mixed biopolymeric micelles, highly promising as drug carriers.
ObjectiveThe present work sought to understand the physicochemical interaction of the antimicrobial peptide TRP3 with the mixed polymeric micelle made from pluronic F127 and the saponin glycyrrhizin.
MethodsThe interaction of tritrpticin with mixed nanostructured micelles was evaluated through fluorescence spectroscopy and fluorescence quenching with acrylamide. The experiments were performed at room temperature (25 ± 1°C), adopting an excitation wavelength set to 280 nm and emission between 300 and 500 nm, with a slit of 5 nm.
ResultsThe interaction of the cationic peptide tritrpticin with the mixed biopolymeric micelles was observed through the blue shift of the fluorescence emission to shorter wavelengths, proving the change of tryptophan to a more hydrophobic environment. Through the fluorescence suppression technique, it was possible to indicate the location of the peptide in the mixed micelles, proving tritrpticin to be partially inserted inside them.
ConclusionIt was concluded that tritrpticin interacted with mixed nanostructured micelles, forming a promising system for biotechnological applications.
-
Volumes & issues
-
Volume 32 (2025)
-
Volume 31 (2024)
-
Volume 30 (2023)
-
Volume 29 (2022)
-
Volume 28 (2021)
-
Volume 27 (2020)
-
Volume 26 (2019)
-
Volume 25 (2018)
-
Volume 24 (2017)
-
Volume 23 (2016)
-
Volume 22 (2015)
-
Volume 21 (2014)
-
Volume 20 (2013)
-
Volume 19 (2012)
-
Volume 18 (2011)
-
Volume 17 (2010)
-
Volume 16 (2009)
-
Volume 15 (2008)
-
Volume 14 (2007)
-
Volume 13 (2006)
-
Volume 12 (2005)
-
Volume 11 (2004)
-
Volume 10 (2003)
-
Volume 9 (2002)
-
Volume 8 (2001)
Most Read This Month
