The point mutation S120G in human nucleoside diphosphate kinase A, identified in patients with neuroblastoma, causes a protein folding defect. The urea-unfolded protein cannot refold in vitro, and accumulates as a molten globule folding intermediate. We show here that the trimethylamine-N-oxide (TMAO) corrects the folding defect and stimulated subunit association. TMAO also substantially increased the stability to denaturation by urea of both wild-type and S120G mutant. A non-native folding intermediate accumulated in the presence of 4.5-7M urea and of 2M TMAO. It was inactive, monomeric, contained some secondary structure but no tertiary structure and displayed a remarkable stability to denaturation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.febslet.2009.01.043 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dihydropyrimidine enzyme activity and its effect on chemotherapy toxicity: importance of genetic testing.
Cancer Chemother Pharmacol
January 2025
Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Purpose: Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.
Case: A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000).
Integrative bioinformatics and machine learning approach unveils potential biomarkers linking coronary atherosclerosis and fatty acid metabolism-associated gene.
J Cardiothorac Surg
January 2025
Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, 257091, Shandong, People's Republic of China.
Background: Atherosclerosis (AS) is increasingly recognized as a chronic inflammatory disease that significantly compromises vascular health and acts as a major contributor to cardiovascular diseases. Advancements in lipidomics and metabolomics have unveiled the complex role of fatty acid metabolism (FAM) in both healthy and pathological states. However, the specific roles of fatty acid metabolism-related genes (FAMGs) in shaping therapeutic approaches, especially in AS, remain largely unexplored and are a subject of ongoing research.
View Article and Find Full Text PDFHypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines.
Clin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
View Article and Find Full Text PDFExploring the anticancer activities of Sulfur and magnesium oxide through integration of deep learning and fuzzy rough set analyses based on the features of Vidarabine alkaloid.
Sci Rep
January 2025
Faculty of Computer and AI, Cairo University, Giza, Egypt.
Drug discovery and development is a challenging and time-consuming process. Laboratory experiments conducted on Vidarabine showed IC 6.97 µg∕mL, 25.
View Article and Find Full Text PDFDecoding the mA epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach.
Nat Commun
January 2025
National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Epitranscriptomic modifications, particularly N6-methyladenosine (mA), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting mA from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations.
View Article and Find Full Text PDFWant 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!