An RWD domain is a well conserved domain found through bioinformatic analysis of the human proteome sequence; however, its function has been unknown. Ubiquitin-like modifications require the catalysis of three enzymes generally known as E1, E2, and E3. We solved the crystal structure of the E2 for the small ubiquitin-like modifiers (SUMO) in complex with an RWD domain and confirmed the structure using solution NMR analysis. The binding surface of RWD on Ubc9 is located near the N terminus of Ubc9 that is known to be involved in noncovalent binding of the proteins in the conjugation machinery, including a domain of E1, SUMO, and an E3 ligase. NMR data indicate that the RWD domain does not bind to SUMO and E1. The interaction between RWD and Ubc9 has a Kd of 32 ± 4 μM. Consistent with the structure and binding affinity and in contrast to a previous report, the RWD domain and RWDD3 have minimal effects on global SUMOylation. The structural and biochemical information presented here forms the basis for further investigation of the functions of RWD-containing proteins.
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http://dx.doi.org/10.1074/jbc.M115.644047 | DOI Listing |
Clin Transl Sci
December 2024
Critical Path Institute, Tucson, Arizona, USA.
In the rapidly evolving landscape of healthcare and drug development, the ability to efficiently collect, process, and analyze large volumes of real-world data (RWD) is critical for advancing drug development. This article provides a blueprint for establishing an end-to-end data and analytics pipeline in a cloud-based environment. The pipeline presented here includes four major components, including data ingestion, transformation, visualization, and analytics, each supported by a suite of Amazon Web Services (AWS) tools.
View Article and Find Full Text PDFAnimal
November 2024
College of Animal Science and Technology, Hebei Agricultural University, Hebei, Baoding 071000, China; The Research Center of Cattle and Sheep Embryonic Technique of Hebei Province, Hebei, Baoding, 071000 Baoding, China. Electronic address:
Sheep litter size is a critical trait in mutton production. While litter size regulation in relation to DNA transcription have been rigorously investigated, the function of RNA editing remains less explored. To elucidate the mechanisms controlling sheep fecundity at the RNA editing level and identify pivotal RNA editing sites, this study scrutinised RNA editing sites (RESs) in follicular and luteal phases of ovaries from sheep with high and low fecundity, and the functions of population-specific RESs were subsequently analysed.
View Article and Find Full Text PDFPharmacoepidemiol Drug Saf
November 2024
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Purpose: The oncology quality, characterization, and assessment of real-world data (Oncology QCARD) Initiative was formed to develop a set of minimum study design and data elements needed to evaluate the fitness of the real-world data (RWD) source(s) proposed in an initial study concept as part of early interaction with scientific reviewers.
Methods: A multidisciplinary executive committee (EC) was established to guide the Oncology QCARD Initiative. The EC conducted a landscape review of published literature, guidances, and guidelines to evaluate relevant dimensions of data quality measurement.
Multidiscip Respir Med
March 2024
National Centre for Respiratory Pharmacoeconomics & Pharmacoepidemiology - CESFAR, Verona.
Inhalation represents the most convenient route for delivering respiratory drugs. Delivery systems showed a huge technological progress and several pocket inhalers had been engineered over the last decades for clinical use. Despite the growing technological efforts aimed to simplify the inhalation procedures and optimize the therapeutic outcomes, the effectiveness of drug inhalation through inhalers still represents a major challenge in respiratory medicine.
View Article and Find Full Text PDFInt J Mol Sci
March 2024
Department of Stress Response Science, Biomedical Research Center, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Aomori, Japan.
GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species.
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