Article
Multidisciplinary Sciences
Rong Shen, Yilin Meng, Benoit Roux, Eduardo Perozo
Summary: This study investigates the conformational changes in voltage-sensing domains (VSDs) during the voltage activation process. Through molecular dynamics simulations and experimental validations, the researchers identified four different conformations visited in the VSD of the phosphatase Ci-VSP. The results provide insights into the energetics and mechanism of voltage activation in VSDs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Rongxing Liu, Wenchao Zhang, Panhong Gou, Jeremy Berthelet, Qing Nian, Guillaume Chevreux, Veronique Legros, Gautier Moroy, Linh-Chi Bui, Li Wang, Jean-Marie Dupret, Frederique Deshayes, Fernando Rodrigues Lima
Summary: PTP1B is a protein target of cisplatin and is inhibited by this drug at molecular, cellular, and in vivo levels. In addition, cisplatin may exert its biological effects through perturbation of cell signaling and other processes.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Medicinal
Guoyi Yan, Xinxin Zhong, Chunlan Pu, Lin Yue, Huifang Shan, Suke Lan, Meng Zhou, Xueyan Hou, Jie Yang, Deyu Li, Shilong Fan, Rui Li
Summary: The development of a rationally designed covalent inhibitor, Con B-1, shows promising potential in selectively targeting ALK with low toxicity to normal cells. Compared to Ceritinib, Con B-1 demonstrates improved anticancer activities and potential antidrug resistant capabilities, making it a promising drug candidate for the treatment of NSCLC. This work provides a new perspective on the design of covalent inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Dhanaji M. Lade, Roxy Nicoletti, James Mersch, Yehenew M. Agazie
Summary: SHP2 is an important oncogene in cancers driven by overexpression of receptor tyrosine kinases. In this study, we developed an optimized derivative BPDA2 as an SHP2 inhibitor with increased potency and selectivity, and demonstrated its efficacy and selectivity in cellular assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Itsumi Tani, Shogo Ito, Yukiko Shirahata, Yutaka Matsuyama, James G. Omichinski, Yasuyuki Shimohigashi, Rui Kamada, Kazuyasu Sakaguchi
Summary: The study investigated the roles of two Arg residues in the metal-dependent protein phosphatase PPM1A on dephosphorylation activity. Results indicated that both Arg residues were crucial for enzymatic activity, with Arg186 positioned to interact with the substrate phosphate group. The significance of each Arg residue in catalysis depended on the specific substrate.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Cong Yong, Yipu Xu, Hui Yu, Peiran Wu, Jiansong Wang, Liu-Liu Shen, Gui-Rong Zhang, Donghai Mei
Summary: ZIF-derived carbons are a new type of non-precious metal catalyst for the oxygen reduction reaction. The smaller the ZDC particle size, the higher the ORR activity, but the exact influence of nitrogen functionalities is still uncertain. This study also reveals a correlation between the ORR activity and the site density of Co-Nx within the ZDC materials.
JOURNAL OF CATALYSIS
(2023)
Article
Agriculture, Multidisciplinary
Yuki Takashima, Kazuki Ishikawa, Rina Miyawaki, Mana Ogawa, Takeshi Ishii, Takumi Misaka, Shoko Kobayashi
Summary: In this study, the polyphenols theaflavin-3-gallate (TF2A) and theaflavin-3'-gallate (TF2B) were identified to significantly inhibit taurocholic acid (TC) uptake in Caco-2 cells by oxidizing their benzotropolone rings and covalently bonding with cysteine residues of ASBT. Their inhibitory effect was also found to be competitive through a substrate concentration-dependent TC uptake assay.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Chemistry, Analytical
Yongbin Zhang, Le Wen, Weijie Zhang, Yongkang Yue, Jianbin Chao, Fangjun Huo, Caixia Yin
Summary: Reactive sulfur species play crucial roles in physiological and pathological processes. A multiple reaction site fluorescent probe was designed to analyze different sulfides, enabling detection of sulfide in mitochondria and imaging in cells and zebrafish. This method offers broad prospects for practical applications.
Article
Infectious Diseases
Gina Nicoletti, Kylie White
Summary: Phylogenetically diverse fungal species are causing severe diseases and deaths, emphasizing the need for new targets and fungicidal drugs. Nitroalkenyl benzene derivatives, including Nitropropenyl benzodioxole (NPBD), show high activity against various fungi and have different patterns of dynamic kill rates. NPBD does not induce resistant or drug tolerant strains and highlights the importance of fungal tyrosine phosphatases and redox thiol molecules as selective targets for antimicrobial drug development. NPBD is a selective antifungal agent with low oral toxicity suitable for local treatment.
Article
Microbiology
Yilin Pang, Jing Wang, Xueping Gao, Mengyao Jiang, Lifei Zhu, Feng Liang, Mengxiang Liang, Xiaolin Wu, Xianxian Xu, Xiaojun Ren, Ting Xie, Wu Wang, Qianqian Sun, Xiaojun Xiong, Jianxin Lyu, Jianghui Li, Guoqiang Tan
Summary: In this study, the fusion of IscS N-terminus with NFS1 C-terminus was conducted, revealing that SUMO-EH-IscS exhibits significant growth recovery and NADH-dehydrogenase I activity in deficient cells. The mutation of IscS resulted in different absorption peaks during the enzyme reaction, indicating that the conserved active site residues play a key role in substrate entry and enzymatic regulation.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Analytical
Di Yuan, Kexin Pan, Suying Xu, Leyu Wang
Summary: In this work, a fluorescent probe with dual channel spectral responses toward human serum albumin (HSA) was designed and synthesized. The probe displayed weak fluorescence but exhibited extensive fluorescence emissions toward HSA. It showed higher selectivity and stronger binding affinity than its counterparts. The probe could also be employed for the recognition of glutathione.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Aiyi Dong, Kun Li, Rentao Mu, Conghui Liu, Rongtan Li, Haoran Jia, Le Lin, Qiang Fu
Summary: The effect of D2O adsorption on D-2 activation over MgO nanocatalysts was investigated using FT-IR and TPD techniques. It was found that two sets of hydride and hydroxyl species produced from D-2 dissociation at more active and less active Mg-O pairs could be observed by FT-IR and desorb via the product of D-2. The physically adsorbed D2O overlayer was found to not affect the dissociation of D-2, as D-2 could pass through the molecular layer and access the surface-active sites.
Article
Chemistry, Multidisciplinary
Shubhajit Das, Ruben Laplaza, J. Terence Blaskovits, Clemence Corminboeuf
Summary: This study reveals that spatial constraints imposed on molecular catalysts can be utilized as a handle to enhance intrinsic activity in bifunctional catalysis. By controlling the geometry of the active site, the catalytic activity of frustrated Lewis pairs (FLPs) in the hydrogenation of CO2 can be greatly increased. This can be achieved by fixing the donor-acceptor centers at specific distances and orientations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Peter M. Heinemann, Daniel Armbruster, Bernhard Hauer
Summary: Active-site loops are crucial for enzyme catalytic properties, but challenging to engineer due to their high flexibility and diversity. The authors identify and engineer hot-spots in the loops of cumene dioxygenase, obtaining variants with altered activity, regio- and enantioselectivity, and present a valuable Linker In Loop Insertion approach for enhanced biocatalysts in the future.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jack A. Collora, Ya-Chi Ho
Summary: HIV-1 integration introduces ectopic transcription factor binding sites into host chromatin, serving as an ectopic enhancer that recruits transcription factors, increases chromatin accessibility, changes 3D chromatin interactions, and enhances gene expression.
Review
Physiology
Yasushi Okamura, Akira Kawanabe, Takafumi Kawai
PHYSIOLOGICAL REVIEWS
(2018)
Review
Neurosciences
Souhei Sakata, Yasushi Okamura
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Biology
Akira Kawanabe, Masaki Hashimoto, Manami Nishizawa, Kazuhisa Nishizawa, Hirotaka Narita, Tomoko Yonezawa, Yuka Jinno, Souhei Sakata, Atsushi Nakagawa, Yasushi Okamura
Article
Physiology
Adisorn Ratanayotha, Takafumi Kawai, Yasushi Okamura
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2019)
Article
Physiology
Akira Kawanabe, Natsuki Mizutani, Onur K. Polat, Tomoko Yonezawa, Takafumi Kawai, Masayuki X. Mori, Yasushi Okamura
JOURNAL OF GENERAL PHYSIOLOGY
(2020)
Article
Multidisciplinary Sciences
Natsuki Mizutani, Akira Kawanabe, Yuka Jinno, Hirotaka Narita, Tomoko Yonezawa, Atsushi Nakagawa, Yasushi Okamura
Summary: This study investigated the electrochemical coupling in Ciona intestinalis VSP using electrophysiology, fluorometry, and structural modeling. It was found that two hydrophobic residues at the bottom of S4 play a crucial role in the VSD-CCR coupling, with the hydrophobic spine acting as a central hub for translating electrical signals into chemical signals in VSP.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Adisorn Ratanayotha, Makoto Matsuda, Yukiko Kimura, Fumiko Takenaga, Tomoaki Mizuno, Md Israil Hossain, Shin-ichi Higashijima, Takafumi Kawai, Michio Ogasawara, Yasushi Okamura
Summary: The findings reveal the crucial role of Vsp protein in regulating endocytosis-dependent nutrient absorption in specialized enterocytes, and provide important insights into the physiological function of Vsp in animal species.
COMMUNICATIONS BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yasushi Okamura, Daisuke Yoshioka
Summary: Many membrane proteins, such as ion channels and ion transporters, are regulated by membrane phospholipids, including phosphoinositides. Voltage-sensing phosphatase (VSP) is a voltage-sensitive phosphoinositide phosphatase that reduces the level of PI(4,5)P2 upon membrane depolarization. VSPs are valuable tools for studying phosphoinositide regulation of ion channels and transporters in cellular electrophysiology, with a focus on Kv7 family potassium channels in this review.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Physiology
Natsuki Mizutani, Yoshifumi Okochi, Yasushi Okamura
PHYSIOLOGICAL REPORTS
(2019)