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Biology
Kangcheng Song, Miao Wei, Wenjun Guo, Li Quan, Yunlu Kang, Jing-Xiang Wu, Lei Chen
Summary: TRPC5 channel is a nonselective cation channel involved in various physiological processes. Inhibitors of TRPC5, such as clemizole and HC-070, stabilize the ion channel in a nonconductive closed state, potentially offering new therapeutic strategies for anxiety disorders, depression, and kidney diseases. The cryo-EM structures of human TRPC5 with inhibitors provide insights into the binding sites and inhibitory mechanisms, facilitating the development of more effective inhibitors targeting TRPC5.
Article
Multidisciplinary Sciences
Fred E. Fregoso, Trevor van Eeuwen, Gleb Simanov, Grzegorz Rebowski, Malgorzata Boczkowska, Austin Zimmet, Alexis M. Gautreau, Roberto Dominguez
Summary: The Arp2/3 complex inhibitor Arpin controls cell migration by interrupting a feedback loop involving Rac-WAVE-Arp2/3 complex. This study reveals the mechanism of Arpin's inhibition through structural, biochemical, and cellular studies. The findings show that Arpin binds to Arp3, a component of the complex, similarly to nucleation-promoting factors (NPFs) that activate the complex. However, Arpin only binds to one site on Arp3, unlike NPFs that bind to two sites. Mutagenesis studies further elucidate the molecular basis for Arpin's inhibition compared to NPFs.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Michael Prattes, Irina Grishkovskaya, Victor-Valentin Hodirnau, Ingrid Roessler, Isabella Klein, Christina Hetzmannseder, Gertrude Zisser, Christian C. Gruber, Karl Gruber, David Haselbach, Helmut Bergler
Summary: The study presents the structure of AAA-ATPase Drg1 in complex with its specific inhibitor diazaborine, shedding light on the mechanism of inhibition and specificity of this type of inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Shabareesh Pidathala, Aditya Kumar Mallela, Deepthi Joseph, Aravind Penmatsa
Summary: The researchers used the Drosophila melanogaster dopamine transporter as a surrogate to study the structure and function of norepinephrine, revealing potential paradigms for designing chronic pain inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sining Sun, Zunyu He, Paul Jiang, Rishika Baral, Maria-Eirini Pandelia
Summary: Type I CRISPR-Cas systems provide protection to prokaryotes by cleaving foreign DNA and regulating pathogenicity and virulence. This study reveals that Cas3 from Thermobifida fusca has significant ssDNA cleavage activity with certain metal ion cofactors and can hydrolyze cyclic mononucleotides, potentially involved in virulence regulation.
Article
Biochemistry & Molecular Biology
Timm O. Koller, Martino Morici, Max Berger, Haaris A. Safdari, Deepti S. Lele, Bertrand Beckert, Kanwal J. Kaur, Daniel N. Wilson
Summary: The antimicrobial peptide drosocin, produced by Drosophila species, is O-glycosylated at threonine 11, and this glycosylation not only affects cellular uptake but also interacts with its target, the ribosome. Cryogenic electron microscopy structures reveal that glycosylated drosocin binds to the polypeptide exit tunnel of the ribosome, interfering with translation termination by trapping RF1 and inducing conformational changes. The glycosylation of drosocin enables multiple interactions with U2609 of 23S rRNA, disrupting a canonical base pair with A752. These findings provide important insights into the interaction of glycosylated drosocin with the ribosome and have implications for the development of antimicrobial drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biology
Iga Kucharska, Lamia Hossain, Danton Ivanochko, Qiren Yang, John L. Rubinstein, Regis Pomes, Jean-Philippe Julien
Summary: This study provides insights into the structural characteristics and antibody interactions of the central repeat region of Plasmodium vivax CSP, which contribute to the development of PvCSP-based vaccines.
Article
Biochemistry & Molecular Biology
Rossitza N. Irobalieva, Ioannis Manolaridis, Scott M. Jackson, Dongchun Ni, Els Pardon, Henning Stahlberg, Jan Steyaert, Kaspar P. Locher
Summary: This study explores the potential of inhibitors targeting sites other than the substrate binding pocket of ABCG2 and develops novel nanobodies as inhibitors. The results show that these nanobodies allosterically bind to different regions of the nucleotide binding domains and prevent the transporter from undergoing conformational changes required for substrate transport.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Elina Cernooka, Janis Rumnieks, Nikita Zrelovs, Kaspars Tars, Andris Kazaks
Summary: Endolysins are enzymes encoded by bacteriophages that have the potential to treat multidrug-resistant bacterial infections. The study found that the endolysin encoded by Hafnia phage Enc34 has an unusual structure and exhibits activity against peptidoglycan from different bacteria. The research also reveals the evolutionary relationship between Enc34 endolysin and other enzymes at the molecular level.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Luca Mazzei, Michele Cianci, Stefano Ciurli
Summary: In this study, the inhibitory characteristics of 1,4-hydroquinone and its derivatives on two ureases were investigated, and the inhibition mechanism was elucidated. Hydroquinone covalently binds to a key residue of urease, resulting in enzyme inactivation. These findings are important for understanding the inhibition mechanism of urease and designing novel antimicrobial agents.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Multidisciplinary Sciences
Larissa Dietz, Cara J. Ellison, Carlos Riechmann, C. Keith Cassidy, F. Daniel Felfoldi, Adan Pinto-Fernandez, Benedikt M. Kessler, Paul R. Elliott
Summary: Certain members of the inhibitor of apoptosis (IAP) family, including BIRC6, regulate cell death by inhibiting caspases, while SMAC antagonizes IAPs and promotes cell death. BIRC6 directly inhibits caspase-3 and-7 and ubiquitinates caspase-3,-7, and-9, working with noncanonical E1, UBA6. SMAC suppresses both mechanisms by competitively displacing caspases.
Article
Microbiology
Tridib Mahata, Shahar Molshanski-Mor, Moran G. Goren, Miriam Kohen-Manor, Ido Yosef, Oren Avram, Dor Salomon, Udi Qimron
Summary: We have identified a novel phage-encoded inhibitor of the major cytoskeletal protein in bacterial division, FtsZ. The inhibition is shown to confer T5 bacteriophage with a growth advantage in dividing hosts. Our studies demonstrate a strategy in bacteriophages to maximize their progeny number by inhibiting escape of one of the daughter cells of an infected bacterium. They further emphasize that FtsZ is a natural target for bacterial growth inhibition.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Kazuto Yoshimi, Kohei Takeshita, Seiya Yamayoshi, Satomi Shibumura, Yuko Yamauchi, Masaki Yamamoto, Hiroshi Yotsuyanagi, Yoshihiro Kawaoka, Tomoji Mashimo
Summary: This article introduces CRISPR-based diagnostics, including Cas12-based DETECTR and Cas13-based SHERLOCK Class 2 CRISPRs, which have been used to detect DNA or RNA from pathogens. A new method called CONAN, using Cas3, is described for rapid, low-cost detection of SARS-CoV-2 and single-base-pair mutations in IAV variants.
Article
Biochemistry & Molecular Biology
Adeline Goulet, Raphaela Joos, Katherine Lavelle, Douwe Van Sinderen, Jennifer Mahony, Christian Cambillau
Summary: This study presents structure predictions of adhesion devices of five representative siphophages infecting Streptococcus thermophilus using AlphaFold2. The predictions reveal the mosaic nature of these devices and identify active sites and residues. Analyzing phage-encoded host adhesion devices with AlphaFold2 should become a standard method for characterizing phage-host interaction machineries and annotating phage genomes reliably.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Emma C. Couves, Scott Gardner, Tomas B. Voisin, Jasmine K. Bickel, Phillip J. Stansfeld, Edward W. Tate, Doryen Bubeck
Summary: This study reveals the role of CD59 in immune regulation, by preventing the formation of MAC toxins through inhibiting the binding of C8 and C9 to the membrane. CD59 also protects membrane integrity by altering the trajectory of C9 beta-hairpins, restricting MAC polymerization. These findings are significant for understanding the dual roles of CD59 in MAC and its involvement in host-pathogen interactions.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Deli Huang, Xinru Zheng, Zi-an Wang, Xin Chen, Wan-ting He, Yingying Zhang, Jin-Gen Xu, Hang Zhao, Wenke Shi, Xin Wang, Yongqun Zhu, Jiahuai Han
MOLECULAR AND CELLULAR BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Xiaofei Wang, Deqiang Yao, Jin-Gen Xu, A-Rong Li, Jianpo Xu, Panhan Fu, Yan Zhou, Yongqun Zhu
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Jianpo Xu, Dandan Xu, Muyang Wan, Li Yin, Xiaofei Wang, Lijie Wu, Yanhua Liu, Xiaoyun Liu, Yan Zhou, Yongqun Zhu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Multidisciplinary Sciences
Yan Zhou, Chunfeng Huang, Li Yin, Muyang Wan, Xiaofei Wang, Lin Li, Yanhua Liu, Zhao Wang, Panhan Fu, Ni Zhang, She Chen, Xiaoyun Liu, Feng Shao, Yongqun Zhu
Article
Biochemistry & Molecular Biology
Jin-Gen Xu, Chunfeng Huang, Zhengfeng Yang, Mengmeng Jin, Panhan Fu, Ni Zhang, Jian Luo, Dali Li, Mingyao Liu, Yan Zhou, Yongqun Zhu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Microbiology
Muyang Wan, Xiaofei Wang, Chunfeng Huang, Dandan Xu, Zhao Wang, Yan Zhou, Yongqun Zhu
NATURE MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Fujie Yan, Chunfeng Huang, Xiaofei Wang, Jiaxing Tan, Sen Cheng, Muyang Wan, Zhao Wang, Shuangyu Wang, Shuhui Luo, Arong Li, Xing Guo, Mingguang Feng, Xiaoyun Liu, Yongqun Zhu, Yan Zhou
Article
Biochemistry & Molecular Biology
Jiaxing Tan, Xing Zhang, Xiaofei Wang, Caihuang Xu, Shenghai Chang, Hangjun Wu, Ting Wang, Huihui Liang, Haichun Gao, Yan Zhou, Yongqun Zhu
Summary: This study provides detailed molecular insights into the structure, assembly, and torque transmission mechanisms of the bacterial flagellar motor.
Article
Biochemistry & Molecular Biology
Jin-gen Xu, Huifeng Jia, Shi Chen, Jingyue Xu, Yifan Zhan, Haijia Yu, Wei Wang, Xi Kang, Xiaopei Cui, Yujie Feng, Xiaofang Chen, Wei Xu, Xianfei Pan, Xiaoyue Wei, Hui Li, Yanting Wang, Simin Xia, Xiaoyan Liu, Lixiang Yang, Yang He, Xiangyang Zhu
Summary: This study developed a novel monoclonal antibody, HB0017, that specifically targets the pro-inflammatory cytokine IL-17A. The antibody effectively antagonized the functions of IL-17A in human and monkey cells and showed therapeutic efficacy in treating inflammatory disorders and psoriasis in a mouse model. It could potentially serve as an alternative biological therapy for patients with inflammation and autoimmune diseases.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)