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Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Chemistry, Physical
Ek Raj Thapaliya, Laetitia Mony, Roberto Sanchez, Benjamin Serraz, Pierre Paoletti, Graham C. R. Ellis-Davies
Summary: Ifenprodil, an important negative allosteric modulator of the NMDA receptor, has been synthesized into caged and photoswitchable derivatives, allowing for selective inhibition of NMDA receptors and manipulation of drug-receptor interactions. The disparity in effectiveness between the two compounds highlights the different capabilities of uncaging and photoswitching in controlling the binding properties of drugs with confined binding sites.
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wu, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wang, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: This study reports a new binding mode between a G protein and its receptor, involving a specific small-molecule agonist. The high-resolution structure of the complex is determined, providing insights for designing small-molecule agonists for class B G-protein-coupled receptors.
Article
Psychiatry
Tsuyoshi Sasaki, Kenji Hashimoto, Tomihisa Niitsu, Yutaka Hosoda, Yasunori Oda, Yuki Shiko, Yoshihito Ozawa, Yohei Kawasaki, Nobuhisa Kanahara, Akihiro Shiina, Tasuku Hashimoto, Takaaki Suzuki, Takeshi Sugawara, Hideki Hanaoka, Masaomi Iyo
Summary: This study suggests that ifenprodil tartrate may be a short-term effective and safe alternative treatment for adolescent patients with PTSD, improving symptoms especially in hyperarousal and dissociation.
PSYCHIATRY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Davia Prischich, Nuria Camarero, Javier Encinar del Dedo, Maria Cambra-Pelleja, Judit Prat, Laura Nevola, Andres Martin-Quiros, Elena Rebollo, Laura Pastor, Ernest Giralt, Maria Isabel Geli, Pau Gorostiza
Summary: Clathrin-mediated endocytosis is a common cellular process in eukaryotes. TL2, a light-regulated peptide inhibitor, can precisely control endocytosis. Interestingly, TL2 retains its inhibitory activity in yeast, even though the corresponding target is not conserved in yeast.
Article
Chemistry, Medicinal
Elena Bechthold, Julian A. Schreiber, Kirstin Lehmkuhl, Bastian Frehland, Dirk Schepmann, Freddy A. Bernal, Constantin Daniliuc, Ines Alvarez, Cristina Val Garcia, Thomas J. Schmidt, Guiscard Seebohm, Bernhard Wuensch
Summary: Ifenprodil, acting as a potent GluN2B-selective NMDA receptor antagonist, demonstrates high affinity and inhibitory activity towards GluN2B-NMDA receptors, especially with the (1R,2R) configuration showing the highest activity and selectivity among the stereoisomers.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Fei Ding, Yunpeng Bai, Qiong Cheng, Shu Yu, Mengchun Cheng, Yulin Wu, Xiaozhe Zhang, Xinmiao Liang, Xiaosong Gu
Summary: The study identified a peptide from Achyranthes bidentata Blume, named bidentatide, as an NMDA receptor subtype 2B (NR2B) antagonist with neuroprotective effects. It showed that bidentatide prevented NMDA-induced cell death and apoptosis through multiple mechanisms, suggesting its potential in developing neuroprotective agents with high selectivity and safety profiles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tsung-Han Chou, Hyunook Kang, Noriko Simorowski, Stephen F. Traynelis, Hiro Furukawa
Summary: NMDARs, mediated by different subtypes, play a fundamental role in brain function and neuropsychiatric disorders. GluN2C and GluN2D subunits have unique structures and functions, and are involved in neuropsychiatric diseases.
Article
Biochemistry & Molecular Biology
Hongnan Liu, Yuwei Zhu, Zebin Lu, Zhiwei Huang
Summary: Bacteriophages have evolved anti-CRISPR proteins (Acrs) to evade the prokaryotic adaptive immune system, and Acrs can serve as switches to regulate gene editing. The crystal structure of the AcrIIA14-SauCas9-sgRNA-dsDNA complex reveals the molecular basis for AcrIIA14 recognition and inhibition, with AcrIIA14 binding to a non-conserved region of SauCas9 HNH domain. This binding triggers conformational allostery in the HNH domain and L1 linker, enhancing the inhibitory ability of AcrIIA14.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Srihari Shankar, Sarath Ramachandran, Nikhil Tulsian, Sridhar Radhakrishnan, Chacko Jobichen, J. Sivaraman
Summary: Glutaminase is a metabolic enzyme that plays a role in cancer cell proliferation. A new allosteric site has been identified in the enzyme, which can be targeted to develop specific inhibitors for the treatment of cancer.
Article
Cell Biology
Swapnil C. Devarkar, Michael Vetick, Shravani Balaji, Ivan B. Lomakin, Luojia Yang, Danni Jin, Wendy V. Gilbert, Sidi Chen, Yong Xiong
Summary: Research has found that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit to restrict host gene expression through translation inhibition. The extensive interactions between MERS-CoV Nsp1 and the mRNA entry channel of the 40S ribosomal subunit are critical for its translation inhibition function, and this mechanism is strikingly similar to SARS-CoV and SARS-CoV-2 Nsp1.
Article
Chemistry, Physical
Y. Zuo, K. Wang, P. Pei, M. Wei, X. Liu, Y. Xiao, P. Zhang
Summary: Zinc is an ideal energy carrier with high energy density, low cost, and environmental friendliness, but the issue of zinc dendrite growth remains unresolved. Understanding the formation mechanism of zinc dendrites is necessary to guide inhibition strategies.
MATERIALS TODAY ENERGY
(2021)
Article
Neurosciences
Xuejin Zhang, Rong Zhang, Jihong Wu
Summary: This study investigates the involvement of the NR2B-PSD95 complex in glaucoma and finds that it plays a role in RGC death. Disrupting the NR2B-PSD95 interaction through drug intervention exerts a neuroprotective effect on RGCs.
Article
Multidisciplinary Sciences
Yange Niu, Rui Liu, Chengcheng Guan, Yuan Zhang, Zhixing Chen, Stefan Hoerer, Herbert Nar, Lei Chen
Summary: Inhibition of hSGLT2 by small-molecule inhibitors such as empagliflozin enhances glucose excretion, which is widely used in clinical settings to manage blood glucose levels in patients with type 2 diabetes. The cryogenic electron microscopy structure of the hSGLT2-MAP17 complex in the empagliflozin-bound state reveals key interactions and provides a basis for future development of new inhibitors targeting these transporters.
Article
Biochemistry & Molecular Biology
Heidi Vitrac, David M. MacLean, Anja Karlstaedt, Heinrich Taegtmeyer, Vasanthi Jayaraman, Mikhail Bogdanov, William Dowhan
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Neurosciences
David M. MacLean, Vasanthi Jayaraman
JOURNAL OF PHYSIOLOGY-LONDON
(2016)
Article
Cell Biology
Sana A. Shaikh, Drew M. Dolino, Garam Lee, Sudeshna Chatterjee, David M. MacLean, Charlotte Flatebo, Christy F. Landes, Vasanthi Jayaraman
Article
Biochemistry & Molecular Biology
Drew M. Dolino, Sudeshna Chatterjee, David M. MacLean, Charlotte Flatebo, Logan D. C. Bishop, Sana A. Shaikh, Christy F. Landes, Vasanthi Jayaraman
NATURE CHEMICAL BIOLOGY
(2017)
Article
Multidisciplinary Sciences
David M. MacLean, Vasanthi Jayaraman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Cell Biology
Ian D. Coombs, David M. MacLean, Vasanthi Jayaraman, Mark Farrant, Stuart G. Cull-Candy
Article
Cell Biology
Jinjun Chen, Lingyong Li, Shao-Rui Chen, Hong Chen, Jing-Dun Xie, Rita E. Sirrieh, David M. MacLean, Yuhao Zhang, Meng-Hua Zhou, Vasanthi Jayaraman, Hui-Lin Pan
Review
Neurosciences
David M. MacLean, Ryan J. Durham, Vasanthi Jayaraman
TRENDS IN NEUROSCIENCES
(2019)
Article
Physiology
Elisa Carrillo, Sana A. Shaikh, Vladimir Berka, Ryan J. Durham, Douglas B. Litwin, Garam Lee, David M. MacLean, Linda M. Nowak, Vasanthi Jayaraman
JOURNAL OF GENERAL PHYSIOLOGY
(2020)
Article
Multidisciplinary Sciences
Ryan J. Durham, Nabina Paudyal, Elisa Carrillo, Nidhi Kaur Bhatia, David M. Maclean, Vladimir Berka, Drew M. Dolino, Alemayehu A. Gorfe, Vasanthi Jayaraman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Matthew L. Rook, Abby Williamson, John D. Lueck, Maria Musgaard, David M. Maclean
Review
Neurosciences
Matthew L. Rook, Maria Musgaard, David M. MacLean
Summary: ASICs are ion channels activated by changes in pH, playing important roles in the nervous system in various physiological and pathophysiological processes. Protons act as neurotransmitters to drive the activation and desensitization of ASICs.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Biology
Tyler Couch, Kyle Berger, Dana L. Kneisley, Tyler W. McCullock, Paul Kammermeier, David M. Maclean
Summary: ASICs are trimeric cation-selective channels activated by decreases in extracellular pH. The coarse topography of chicken ASIC1 intracellular domains was determined by fluorescence resonance energy transfer (FRET), showing the C terminal tail projecting into the cytosol by approximately 35 angstrom. No relative movement between the N and C tails upon extracellular acidification was detected, but axial motions of the membrane proximal segments toward the plasma membrane were observed.
Article
Biochemistry & Molecular Biology
Matthew L. Rook, Tyler W. McCullock, Tyler Couch, John D. Lueck, David M. MacLean
Summary: Acid-sensing ion channels (ASICs) play a crucial role in detecting extracellular acidification in the brain and body. Through studying the collapse and mobility of the acidic pocket, it is found that the collapse of the acidic pocket is not essential for channel activation but influences the stability of the open state of the pore.
Article
Physiology
Matthew L. Rook, Megan Miaro, Tyler Couch, Dana L. Kneisley, Maria Musgaard, David M. MacLean
Summary: Desensitization is a common feature in ASIC ion channels, but the Q276G mutation does not have a significant impact in both human and chicken ASIC1, showing unexpected differences compared to previous findings.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)