Article
Biochemistry & Molecular Biology
Ling-Yun Qin, Zhou Gong, Kan Liu, Xu Dong, Chun Tang
Summary: This study investigates the phosphorylation of Ub by PINK1 at S65 and its interaction with UBA domains of proteasomal shuttle factors. The research reveals that Ubqln2-UBA binds more tightly to pUb than Rad23A, selectively enriching the pUb(RL) conformation. The findings suggest a kinetic constraint in the interaction between Ub and UBA, influencing the functional state of proteasomal shuttle factors.
Review
Biochemistry & Molecular Biology
Wojciech Bialek, James F. Collawn, Rafal Bartoszewski
Summary: This article discusses the role of ubiquitin-mediated protein destabilization in protein degradation, as well as the significance of the ubiquitin-independent pathway and 20S proteasome. It also explores the interaction between the ubiquitin-proteasome system and pathogenic microorganisms, and how these microorganisms manipulate the system to evade or counteract host responses.
Article
Environmental Sciences
Jianan Sun, Valliappan Karuppiah, Yaqian Li, Sivakumar Pandian, Subramanian Kumaran, Jie Chen
Summary: This study cloned thirty-nine cytochrome P450 genes from the T. atroviride T23 genome, with 21 of them being involved in xenobiotic degradation. The quantitative expression of these genes showed different patterns in the presence of dichlorvos at varying concentrations. Specifically, the deletion of TaCyp548-2 reduced the concentration of 2,2-dichloroethanol, indicating its role in the degradation process.
Article
Chemistry, Physical
Nico D. Fessner, Christopher Grimm, Matic Srdic, Hansjoerg Weber, Wolfgang Kroutil, Ulrich Schwaneberg, Anton Glieder
Summary: This study explores the synthetic potential of human P450 3A4 in diversifying natural product classes, resulting in the identification of 31 authentic human metabolites. With efficient expression levels in P. pastoris, this biocatalyst shows promising results for modifying natural products in a one-step fashion.
Article
Biophysics
Kevin F. dos Santos, Elsa M. Materon, Osvaldo N. Oliveira Jr
Summary: This study investigated the influence of cytochrome P450 3A4 (CYP3A4) on the interaction between the drug doxorubicin (DOX) and cell membranes. The results showed that the lipid composition plays a crucial role in this interaction, and that the presence of CYP3A4 significantly reduces the effect of DOX on the cell membranes. These findings support the idea that CYP3A4 is involved in drug resistance and suggest potential strategies to enhance the efficacy of chemotherapy.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Biochemistry & Molecular Biology
Petar M. Mitrasinovic
Summary: The study revealed that chrysin has the largest inhibitory effect on CYP3A4, while quercetin and flavopiridol serve as representative examples of structurally different flavonoids. The inhibition parameters for these compounds were evaluated using the calibrated QM/MM strategy, aiding in quantitatively understanding the functional behavior of the whole flavonoid family. Additionally, a kinetic threshold for further assessment of the time-dependent inhibition of CYP3A4 by flavonoids was explored.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Cell Biology
James L. Shen, Tina M. Fortier, Ruoxi Wang, Eric H. Baehrecke
Summary: Defects in autophagy can lead to issues in metabolism, development, and disease. The loss of Vps13D affects mitophagy, regulated by the core autophagy machinery. Pink1 and Vps13D play roles in Pink1-dependent mitophagy, with Park contributing to mitochondrial clearance through a pathway parallel to Vps13D.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ido Livneh, Victoria Cohen-Kaplan, Bertrand Fabre, Ifat Abramovitch, Lulu Chen, Nishanth Belugali Nataraj, Ikrame Lazar, Tamar Ziv, Yosef Yarden, Yaniv Zohar, Eyal Gottlieb, Aaron Ciechanover
Summary: This study reveals the importance of proteasome translocation in response to amino acid starvation. The translocation is regulated by specific amino acids that activate mTOR signaling pathway. Proteasome translocation stimulates cytosolic proteolysis to replenish amino acids and promote cell survival. This newly identified pathway plays a key role in stress response.
Article
Biochemistry & Molecular Biology
Zhefan Stephen Chen, Mingqi Yan, Wenhui Pei, Bowen Yan, Caoxing Huang, Ho Yin Edwin Chan
Summary: In this study, the potential therapeutic effect of lignin-carbohydrate complexes (LCCs) on polyglutamine diseases was investigated. LCCs isolated from bamboo and poplar were found to effectively eliminate protein aggregation and rescue photoreceptor degeneration. Mechanistically, LCCs were shown to upregulate proteasomal activity, which was crucial for their beneficial effects on polyglutamine neurotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Medicinal
Shiwei Lu, Feng Zhang, Jiahao Gong, Jian Huang, Guanghao Zhu, Yitian Zhao, Qi Jia, Yiming Li, Bo Li, Kaixian Chen, Weiliang Zhu, Guangbo Ge
Summary: This study discovered potent and orally active hCYP3A4 inhibitors from chalcone derivatives and tested their effects on hCYP3A4 in vitro and in vivo. The isoquinoline chalcones were found to have excellent anti-hCYP3A4 effects after screening and optimization. SAR studies revealed the structural requirements for enhancing the anti-CYP3A4 effect. A lead compound, C6, was identified as the most potent hCYP3A4 inhibitor and showed good metabolic stability and safety profiles. In vivo tests demonstrated the efficacy of C6 in increasing drug exposure and prolonging drug half-life. Overall, this study offers valuable insights into developing novel CYP3A4 inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Suganya Sekaran, Soyeon Park
Summary: The proteasome holoenzyme is a complex molecular machine that degrades most proteins. The assembly of the heterohexameric Rpt ring, a crucial part of the proteasome holoenzyme, is regulated by the release of a specific chaperone, Nas2, which ensures proper Rpt ring assembly. Nas2 acts by blocking premature progression of the assembly and can activate an assembly checkpoint to ensure the composition and functional competence of the proteasomal ATPase. This study provides insights into the mechanisms involved in the assembly of the proteasome holoenzyme.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Julianna R. Cresti, Abramo J. Manfredonia, Christopher E. Braganca, Joseph A. Boscia, Christina M. Hurley, Mary D. Cundiff, Daniel A. Kraut
Summary: The 26S proteasome, responsible for protein degradation in eukaryotic cells, transitions between substrate-accepting and substrate-processing conformations, with important intramolecular interactions stabilizing these conformations. A new conformationally sensitive assay revealed that interactions involving Rpn5 and Rpn2 are crucial for stabilizing substrate-processing conformations, impacting the proteasome's ability to successfully unfold and degrade difficult substrates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Seung Han Son, Min Young Kim, Young Su Lim, Hyeon Cheol Jin, June Ho Shin, Jae Kyu Yi, Sungwoo Choi, Mi Ae Park, Ji Hyung Chae, Ho Chul Kang, Young Jin Lee, Vladimir N. Uversky, Chul Geun Kim
Summary: This study uncovers a novel mechanism of CP2c degradation through SUMO1/PSME3/20S proteasome pathway and its significance in cell cycle progression.
Article
Chemistry, Analytical
Michael Riffle, Michael R. Hoopmann, Daniel Jaschob, Guo Zhong, Robert L. Moritz, Michael J. MacCoss, Trisha N. Davis, Nina Isoherranen, Alex Zelter
Summary: The study introduces Magnum and Limelight, an algorithm and software package for the identification and visualization of xenobiotic-protein adducts. Through validation and application, the methods and software enable accurate identification of xenobiotic-protein adducts and fill the gap in comprehensive data visualization tools in the field of open-mass searching.
ANALYTICAL CHEMISTRY
(2022)