Article
Plant Sciences
Belen Rombola-Caldentey, Imelda Mendoza, Francisco J. Quintero, Jose M. Pardo
Summary: Cation/Proton Antiporters (CPA) in all biological membranes regulate cell and intracellular organelle volume and pH. This study focused on the structure-function relationships and activity of the tonoplast-localized NHX1 antiporter in Arabidopsis, which plays a crucial role in K+ accumulation in plant vacuoles. By mutating conserved residues and testing the resulting protein variants in yeast, the researchers found that certain amino acid replacements had minimal impact on the activity of NHX1. However, attempts to alter the electroneutrality of NHX1 resulted in inactive or partly active proteins with varying abilities to control yeast vacuolar pH.
Article
Biology
Vikram Bhatia, Saeid Maghsoudi, Martha Hinton, Anjali Y. Y. Bhagirath, Nisha Singh, Appalaraju Jaggupilli, Prashen Chelikani, Shyamala Dakshinamurti
Summary: This study investigated the structure of adenylyl cyclase 6 and its interactions with forskolin. Mutations were made to identify the amino acids responsible for activating the enzyme. The findings could contribute to the design of selective activators for adenylyl cyclase 6.
Article
Plant Sciences
Minh Thi Thanh Hoang, Diego Almeida, Sandrine Chay, Carine Alcon, Claire Corratge-Faillie, Catherine Curie, Stephane Mari
Summary: AtDTX25, identified as a vacuolar ascorbate transporter in plants, plays a crucial role in regulating the storage and remobilization of iron during seed development. Its function in mediating ascorbate efflux helps promote the reduction and release of Fe3+ to support seedling growth.
Article
Plant Sciences
Xia Li, Geng Chen, Qing-Qing Gao, Chun-Fan Xiang, Cheng-Xiao Yuan, Xiao-Ning Li, Yan-Yu Shu, Guang-Hui Zhang, Yan-Li Liang, Sheng-Chao Yang, Chen-Xi Zhai, Yan Zhao
Summary: This study explored the key enzymes involved in cucurbitacins biosynthesis in the Chinese traditional medicinal plant Hemsleya chinensis. Using AlphaFold2 and molecular docking, the researchers successfully predicted the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments identified three key amino acid residues, E246, M261, and D490, which significantly affected the activity of HcOSC6. This study not only characterized three potential key residues for producing cucurbitacins, but also provided insights into their significant role in metabolic engineering.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Ziyi Yang, Ryan S. Wang, Billy Y. Cheng, Vincent Ruan, Piju Yang, Chen-Hsien Liang, Claire R. Shen
Summary: This study identified two critical residues, M185 and V402, of the flavin-containing monooxygenase from Corynebacterium glutamicum (CgFMO) and generated variants with enhanced indole hydroxylation activity. The best performing mutant M185L/V402A exhibited nearly 10 fold higher catalytic efficiency and greater improvement in the kcat level compared to wild type CgFMO. The study provides insight into the CgFMO active site and aids in the future design of FMO biocatalysts.
BIOCHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Flora Szeri, Valentina Corradi, Fatemeh Niaziorimi, Sylvia Donnelly, Gwenaelle Conseil, Susan P. C. Cole, D. Peter Tieleman, Koen van de Wetering
Summary: ABCC6 inactivating mutations cause the rare hereditary mineralization disorder pseudoxanthoma elasticum. ABCC6 is proposed to be an ATP-dependent ATP efflux pump, with a potential ATP-binding site in its substrate-binding cavity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Kaikai Qiao, Jiaoyan Lv, Lingling Chen, Yanwen Wang, Lina Ma, Jin Wang, Zhe Wang, Long Wang, Qifeng Ma, Shuli Fan
Summary: This study investigated the sugar transporter protein (STP) family in cotton and identified GhSTP18 as an important protein involved in salt stress. Bioinformatic analysis divided cotton STP proteins into four subgroups and transcriptomic data analysis revealed sink-specific expression of 29 GhSTP genes. Quantitative real time-polymerase chain reaction analysis showed that GhSTP18 expression was induced by salt, heat, cold, and drought treatments. Suppression of GhSTP18 decreased cotton's sensitivity to salt stress, suggesting its negative regulation of salt tolerance.
PHYSIOLOGIA PLANTARUM
(2023)
Article
Biochemistry & Molecular Biology
Hyunjong Byun, Jiyeon Park, Benedict U. Fabia, Joshua Bingwa, Mihn Hieu Nguyen, Haeshin Lee, Jung Hoon Ahn
Summary: This study provides a method to rescue secretion by correcting secretion-blocking regions, making a significant step in understanding the physiological properties of ABC transporter-dependent protein secretion and laying the foundation for the development of a secretion-based protein-producing platform.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Ali Movahedi, Hui Wei, Xiaohong Zhou, Jake C. Fountain, Zhong-Hua Chen, Zhiying Mu, Weibo Sun, Jiaxin Zhang, Dawei Li, Baozhu Guo, Rajeev K. Varshney, Liming Yang, Qiang Zhuge
Summary: This study demonstrates that simultaneous inhibition of NHEJ and overexpression of HDR enhancer factors can greatly improve the efficiency of gene knock-in in plants. This approach may have potential applications in not only plants but also mammals for enhancing CRISPR-mediated gene modification efficiency.
HORTICULTURE RESEARCH
(2022)
Article
Biochemical Research Methods
John D. Lapek, Zhenze Jiang, Jacob M. Wozniak, Elena Arutyunova, Steven C. Wang, M. Joanne Lemieux, David J. Gonzalez, Anthony J. O'Donoghue
MOLECULAR & CELLULAR PROTEOMICS
(2019)
Review
Chemistry, Multidisciplinary
Ana-Nicoleta Bondar, M. Joanne Lemieux
Article
Biochemistry & Molecular Biology
Zhenlin Ouyang, Jan Felix, Jinhong Zhou, Yingmei Pei, Bohan Ma, Peter M. Hwang, M. Joanne Lemieux, Irina Gutsche, Fang Zheng, Yurong Wen
Review
Chemistry, Medicinal
Rui Chen, Aravindhan Ganesan, Isobel Okoye, Elena Arutyunova, Shokrollah Elahi, M. Joanne Lemieux, Khaled Barakat
MEDICINAL RESEARCH REVIEWS
(2020)
Article
Biophysics
John Paul Glaves, Joseph O. Primeau, Przemek A. Gorski, L. Michel Espinoza-Fonseca, M. Joanne Lemieux, Howard S. Young
BIOPHYSICAL JOURNAL
(2020)
Review
Biochemistry & Molecular Biology
Laine Lysyk, Raelynn Brassard, Nicolas Touret, M. Joanne Lemieux
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Neurosciences
Wentong Long, Mohammad Fatehi, Shubham Soni, Rashmi Panigrahi, Koenraad Philippaert, Yi Yu, Rees Kelly, Brett Boonen, Amy Barr, Dominic Golec, Scott A. Campbell, Katarina Ondrusova, Matt Hubert, Troy Baldwin, M. Joanne Lemieux, Peter E. Light
JOURNAL OF PHYSIOLOGY-LONDON
(2020)
Article
Multidisciplinary Sciences
Wayne Vuong, Muhammad Bashir Khan, Conrad Fischer, Elena Arutyunova, Tess Lamer, Justin Shields, Holly A. Saffran, Ryan T. McKay, Marco J. van Belkum, Michael A. Joyce, Howard S. Young, D. Lorne Tyrrell, John C. Vederas, M. Joanne Lemieux
NATURE COMMUNICATIONS
(2020)
Editorial Material
Biochemistry & Molecular Biology
M. Joanne Lemieux, Michael Overduin
Summary: The field of membrane structural biology is rapidly evolving, with developments such as native nanodiscs and memteins changing the way we understand biological membranes. Tools like cryo-electron microscopy, X-ray crystallography, and nuclear magnetic resonance spectroscopy are advancing, but challenges remain in understanding how lipids and ligands interact at an atomic level.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Chemistry, Medicinal
Bing Bai, Alexandr Belovodskiy, Mostofa Hena, Appan Srinivas Kandadai, Michael A. Joyce, Holly A. Saffran, Justin A. Shields, Muhammad Bashir Khan, Elena Arutyunova, Jimmy Lu, Sardeev K. Bajwa, Darren Hockman, Conrad Fischer, Tess Lamer, Wayne Vuong, Marco J. van Belkum, Zhengxian Gu, Fusen Lin, Yanhua Du, Jia Xu, Mohammad Rahim, Howard S. Young, John C. Vederas, D. Lorne Tyrrell, M. Joanne Lemieux, James A. Nieman
Summary: This study describes novel antiviral compounds against coronaviruses, which have good activity and stability, and show effective inhibition of SARS-CoV-2 replication. They also exhibit better selectivity index and broad-spectrum antiviral activity against different types of coronaviruses.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Elena Arutyunova, Muhammad Bashir Khan, Conrad Fischer, Jimmy Lu, Tess Lamer, Wayne Vuong, Marco J. van Belkum, Ryan T. McKay, D. Lorne Tyrrell, John C. Vederas, Howard S. Young, M. Joanne Lemieux
Summary: The main protease of SARS-CoV-2 is a high priority drug target, and GC376 has been shown to effectively inhibit it. GC376 also demonstrates reversible binding and broad specificity, making it suitable for clinical trials. The stability and thermodynamic parameters of the protease were studied, revealing insights into the physical chemical properties of viral enzymes.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biology
M'Lynn E. Fisher, Elisa Bovo, Rodrigo Aguayo-Ortiz, Ellen E. Cho, Marsha P. Pribadi, Michael P. Dalton, Nishadh Rathod, M. Joanne Lemieux, L. Michel Espinoza-Fonseca, Seth L. Robia, Aleksey Zima, Howard S. Young
Summary: DWORF has been identified as a direct activator of SERCA, increasing its turnover rate and promoting calcium reuptake in the absence of phospholamban. Fluorescence resonance energy transfer experiments revealed that DWORF has a higher affinity for SERCA in the presence of calcium.
Article
Chemistry, Medicinal
Wayne Vuong, Conrad Fischer, Muhammad Bashir Khan, Marco J. van Belkum, Tess Lamer, Kurtis D. Willoughby, Jimmy Lu, Elena Arutyunova, Michael A. Joyce, Holly A. Saffran, Justin A. Shields, Howard S. Young, James A. Nieman, D. Lorne Tyrrell, M. Joanne Lemieux, John C. Vederas
Summary: The study demonstrates that GC376 and its derivatives are effective inhibitors of Mpro in SARS-CoV-2, with improved affinity and therapeutic index. Crystallographic analysis reveals an alternative binding pocket in M-pro and the mechanism of alternative binding induced by polar groups or a nearby methyl. Additionally, new findings on solubility and colloidal formation in aqueous media are reported, along with the use of choline to increase solubility.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Laine Lysyk, Raelynn Brassard, Elena Arutyunova, Verena Siebert, Zhenze Jiang, Emmanuella Takyi, Melissa Morrison, Howard S. Young, Marius K. Lemberg, Anthony J. O'Donoghue, M. Joanne Lemieux
Summary: This study using recombinant PARL provides fundamental insights into its catalytic activity and substrate preferences, enhancing our understanding of its role in mitochondrial function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xiaocen Lu, Yurong Wen, Shuce Zhang, Wei Zhang, Yilun Chen, Yi Shen, M. Joanne Lemieux, Robert E. Campbell
Summary: The research team discovered and developed PhoCl2c and PhoCl2f, two variants with significant improvements in photocleavage rate, enabling more effective control of biomolecular activities in cells. The performance of these new variants was confirmed through X-ray crystal structures analysis and molecular dynamics simulations.