Article
Biochemistry & Molecular Biology
Gerard H. M. Huysmans, Didar Ciftci, Xiaoyu Wang, Scott C. Blanchard, Olga Boudker
Summary: Membrane transporters facilitate the uptake of nutrients, signaling molecules, and drugs into cells. However, the structural features determining their rates are largely unknown. A study on the archaeal model glutamate transporter homologue Glt(Ph) from Pyrococcus horikoshii revealed that the high-energy transition state of the transporter limits the rate of substrate translocation, providing insights for the search of allosteric modulators.
Article
Physiology
Krishna D. Reddy, Didar Ciftci, Amanda J. Scopelliti, Olga Boudker
Summary: This study investigates an archaeal homologue, Glt(Ph), and finds that a mutant Glt(Ph) exhibits slow equilibrium between at least two substates with different substrate binding affinities. Wild type Glt(Ph) shows similar binding properties, and the modulation of substate equilibrium correlates with transport rates. Cryo-EM analysis reveals structural classes with perturbed helical packing near the binding site, suggesting that subtle structural differences distinguish transporter subpopulations with different dynamic properties.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Valentina Arkhipova, Haigen Fu, Mark W. H. Hoorens, Gianluca Trinco, Lucien N. Lameijer, Egor Marin, Ben L. Feringa, Gerrit J. Poelarends, Wiktor Szymanski, Dirk J. Slotboom, Albert Guskov
Summary: Photopharmacology addresses drug selectivity and side effects through the creation of light-activated photoresponsive molecules. However, the structural basis for light-induced modulation of inhibitory potency is still unclear, posing a major design challenge for this emerging field. Crystal structures of glutamate transporter homologue Glt(Tk) with photoresponsive inhibitors provide insight into the origins of photocontrol and lay the foundation for using photocontrolled ligands to study transporter dynamics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Mu Li, Xintong Zhang, Sixiang Chen, Hanhe Liu, Yuan-Wei Zhang
Summary: This study reveals a novel structural characteristic of the neurotransmitter sodium symporter (NSS) family, specifically in TuriSERT, and demonstrates the unique substrate binding site and 1:1 stoichiometry of sodium-substrate binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Samir Batarni, Nanda Nayak, Audrey Chang, Fei Li, Surabhi Hareendranath, Lexi Zhou, Hongfei Xu, Robert Stroud, Jacob Eriksen, Robert H. Edwards
Summary: The solute carrier 17 family uses two different modes of coupling to transport diverse organic anions. Some transporters are driven by membrane potential and regulated by H+ and Cl-, while others couple organic anion flux to co-transport of H+. The study of Escherichia coli DgoT, a H+/galactonate cotransporter, reveals that specific residues play a crucial role in substrate recognition and proton translocation. The findings also suggest that the translocation of protons occurs in series and that a highly conserved glutamate residue is central to the coupling of H+ by DgoT.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Tomoka Gose, Heather M. Aitken, Yao Wang, John Lynch, Evadnie Rampersaud, Yu Fukuda, Medb Wills, Stefanie A. Baril, Robert C. Ford, Anang Shelat, Megan L. O' Mara, John D. Schuetz
Summary: This research reveals the mechanism of substrate selection by ABCG2, identifying a crucial residue N436 that acts as a discriminator for substrate recognition and is required for optimal inhibitor action.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Tian Xie, Zike Zhang, Qi Fang, Bowen Du, Xin Gong
Summary: The cryo-EM structures of human retinal ABCA4 transporter, in apo state, in complex with ATP, or with the physiological lipid substrate N-retinylidene-phosphatidylethanolamine (NRPE), reveal lateral opening, substrate recognition, and suggest a common 'lateral access and extrusion' mechanism for ABCA-mediated lipid transport.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Zhenglai Zhang, Huiwen Chen, Ze Geng, Zhuoya Yu, Hang Li, Yanli Dong, Hongwei Zhang, Zhuo Huang, Juquan Jiang, Yan Zhao
Summary: In this study, cryo-EM structures of human EAAT2 in complexes with glutamate or selective inhibitor WAY-213613 were reported, providing important insights into substrate recognition and selective inhibition.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Elise Kaplan, Nicholas P. Greene, Abigail E. Jepson, Vassilis Koronakis
Summary: In gram-negative bacteria, the Lol system plays a vital role in transporting triacylated lipoproteins from the inner membrane to the outer membrane. LolA, the periplasmic chaperone protein, is crucial for this process. This study presents the crystal structure of liganded LolA, providing molecular details of lipoprotein association and demonstrating how LolA accommodates different lipoproteins by interacting with their acyl chains. Additionally, the comparison of LolA structures reveals that the insertion of lipoprotein acyl chains disrupts the interaction between LolA and LolC. These findings contribute to a better understanding of the trafficking pathway in gram-negative bacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Ying Huang, Chenyang Xue, Liangdong Wang, Ruiqian Bu, Jianqiang Mu, Yong Wang, Zhongmin Liu
Summary: This study uses cryo-EM to resolve the structures of hMRP4 in different states, including apo inward-open, ATP-bound outward-open, PGE1 substrate-bound, and sulindac inhibitor-bound states. The findings reveal the competition between substrate and inhibitor for the same binding pocket and provide insights into the transport and inhibition mechanism of hMRP4, which have implications for drug development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Dongmei Mai, Rongqing Chen, Ji Wang, Jiawei Zheng, Xiuping Zhang, Shaogang Qu
Summary: This study investigated the role of 14 crucial amino acid residues in TM2 of EAAT2, finding that mutations in these residues affect the localization, substrate affinity, and activity of EAAT2, thereby influencing its transporter function.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Kotaro Anamizu, Ryuichi Takase, Mamoru Hio, Daisuke Watanabe, Bunzo Mikami, Wataru Hashimoto
Summary: This study determined the different conformations of SPH1118 through X-ray crystallography, revealing its binding mechanism and conformational changes in response to substrate for pectin chemotaxis and assimilation. It is the first study to elucidate how a solute-binding protein with dual functions recognizes the substrate through flexible conformational changes in response to substrate size.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Organic
Kyoka Sakamoto, Hajime Sato, Masanobu Uchiyama
Summary: In this study, we conducted a detailed scrutiny of the biosynthetic pathways of asperterpenol/preasperterpenoid based on comprehensive DFT calculations and proposed relevant conclusions.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Waqas Javed, Sylvain Vallet, Marie-Pierre Clement, Aline Le Roy, Martine Moulin, Michael Hartlein, Cecile Breyton, Odile Burlet-Schiltz, Julien Marcoux, Cedric Orelle, Christine Ebel, Anne Martel, Jean-Michel Jault
Summary: This study used small angle neutron scattering and hydrogen/deuterium exchange coupled to mass spectrometry to investigate the conformational states of the BmrA transporter during its ATPase cycle. The researchers found that under specific mutation conditions, the BmrA transporter can be trapped in an ATP-bound inward-facing conformation. Comparing the transition-like state induced by vanadate with the apo state or the presence of ADP/Mg, it was observed that in the post-hydrolytic step, the distances between the two nucleotide-binding domains appeared to be more separated but remained shorter than in the widest opening state found in the related transporter MsbA.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chen Wang, Leiye Yu, Jiying Zhang, Yanxia Zhou, Bo Sun, Qingjie Xiao, Minhua Zhang, Huayi Liu, Jinhong Li, Jialu Li, Yunzi Luo, Jie Xu, Zhong Lian, Jingwen Lin, Xiang Wang, Peng Zhang, Li Guo, Ruobing Ren, Dong Deng
Summary: The study presents cryo-EM structures of PfENT1, revealing its role as an inosine transporter and describing the inhibitory mechanism of the endofacial inhibitor, GSK4. PfENT1 is essential for nucleoside uptake in Plasmodium falciparum, which lacks de novo purine biosynthesis enzymes. Specific inhibitors of PfENT1 show potential for preventing the proliferation of the parasite. This research provides valuable insights into the substrate recognition and inhibitory mechanisms of PfENT1, which will aid in the development of antimalarial drugs.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Shana Bergman, Asghar Razavi, George Khelashvili, Harel Weinstein
Article
Biochemistry & Molecular Biology
Yun Huang, Xiaoyu Wang, Guohua Lv, Asghar M. Razavi, Gerard H. M. Huysmans, Harel Weinstein, Clay Bracken, David Eliezer, Olga Boudker
NATURE CHEMICAL BIOLOGY
(2020)
Correction
Biochemical Research Methods
Ismael Rodriguez-Espigares, Mariona Torrens-Fontanals, Johanna K. S. Tiemann, David Aranda-Garcia, Juan Manuel Ramirez-Anguita, Tomasz Maciej Stepniewski, Nathalie Worp, Alejandro Varela-Rial, Adrian Morales-Pastor, Brian Medel-Lacruz, Gaspar Pandy-Szekeres, Eduardo Mayol, Toni Giorgino, Jens Carlsson, Xavier Deupi, Slawomir Filipek, Marta Filizola, Jose Carlos Gomez-Tamayo, Angel Gonzalez, Hugo Gutierrez-de-Teran, Mireia Jimenez-Roses, Willem Jespers, Jon Kapla, George Khelashvili, Peter Kolb, Dorota Latek, Maria Marti-Solano, Pierre Matricon, Minos-Timotheos Matsoukas, Przemyslaw Miszta, Mireia Olivella, Laura Perez-Benito, Davide Provasi, Santiago Rios, Ivan R. Torrecillas, Jessica Sallander, Agnieszka Sztyler, Silvana Vasile, Harel Weinstein, Ulrich Zachariae, Peter W. Hildebrand, Gianni De Fabritiis, Ferran Sanz, David E. Gloriam, Arnau Cordomi, Ramon Guixa-Gonzalez, Jana Selent
Article
Biochemical Research Methods
Ismael Rodriguez-Espigares, Mariona Torrens-Fontanals, Johanna K. S. Tiemann, David Aranda-Garcia, Juan Manuel Ramirez-Anguita, Tomasz Maciej Stepniewski, Nathalie Worp, Alejandro Varela-Rial, Adrian Morales-Pastor, Brian Medel-Lacruz, Gaspar Pandy-Szekeres, Eduardo Mayol, Toni Giorgino, Jens Carlsson, Xavier Deupi, Slawomir Filipek, Marta Filizola, Jose Carlos Gomez-Tamayo, Angel Gonzalez, Hugo Gutierrez-de-Teran, Mireia Jimenez-Roses, Willem Jespers, Jon Kapla, George Khelashvili, Peter Kolb, Dorota Latek, Maria Marti-Solano, Pierre Matricon, Minos-Timotheos Matsoukas, Przemyslaw Miszta, Mireia Olivella, Laura Perez-Benito, Davide Provasi, Santiago Rios, Ivan R. Torrecillas, Jessica Sallander, Agnieszka Sztyler, Silvana Vasile, Harel Weinstein, Ulrich Zachariae, Peter W. Hildebrand, Gianni De Fabritiis, Ferran Sanz, David E. Gloriam, Arnau Cordomi, Ramon Guixa-Gonzalez, Jana Selent
Article
Computer Science, Interdisciplinary Applications
Tu Mai Anh Do, Loic Pottier, Silvina Caino-Lores, Rafael Ferreira da Silva, Michel A. Cuendet, Harel Weinstein, Trilce Estrada, Michela Taufer, Ewa Deelman
Summary: Performance evaluation is crucial for understanding the behavior of scientific workflows, especially in dealing with in situ workflows. By proposing a lightweight metric, the resource usage efficiency of in situ workflow execution can be assessed, analyzing the tradeoffs of various configurable parameters and evaluating different execution scenarios.
JOURNAL OF COMPUTATIONAL SCIENCE
(2021)
Article
Biophysics
George Khelashvili, Ambrose Plante, Milka Doktorova, Harel Weinstein
Summary: Studies have shown that the fusion peptide (FP) of coronaviruses requires binding of Ca2+ ions to enhance penetration, but the mechanisms of membrane insertion and destabilization remain unclear.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemical Research Methods
Hector Carrillo-Cabada, Jeremy Benson, Asghar M. Razavi, Brianna Mulligan, Michel A. Cuendet, Harel Weinstein, Michela Taufer, Trilce Estrada
Summary: To successfully predict a protein's function, techniques that maintain its 3D information while performing at scale are necessary. Researchers extended a protein representation and neural network architecture, demonstrating applicability in protein function prediction and detection of conformational changes in protein trajectories.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ambrose Plante, Harel Weinstein
Summary: Molecular Dynamics (MD) simulations are vital tools for ligand discovery and design, but the challenges of handling large datasets and rare events in complex molecular machines remain. A protocol called Rare Event Detection (RED) has been developed to efficiently detect functionally relevant responses to ligand binding, offering new insights into drug activity.
Article
Multidisciplinary Sciences
George R. Heath, Ekaterina Kots, Janice L. Robertson, Shifra Lansky, George Khelashvili, Harel Weinstein, Simon Scheuring
Summary: This study introduces a new technique called localization AFM (LAFM) that overcomes traditional AFM resolution limits by applying localization image reconstruction algorithms, allowing for structural analysis of biomolecules at the single-molecule level.
Meeting Abstract
Biophysics
George Khelashvili, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina Kots, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina D. Kots, Derek M. Shore, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ambrose Plante, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Pathology
A. Sboner, A. Sigaras, J. Davis, S. Roshal, D. Wilkes, C. Hebding, D. Bockelman, T. Kane, S. Ackermann, M. Sigouros, J. Catalano, M. Martin, W. Song, J. Mosquera, C. Sternberg, M. Loda, H. Weinstein, O. Elemento
JOURNAL OF MOLECULAR DIAGNOSTICS
(2020)
Meeting Abstract
Biophysics
Ekaterina D. Kots, Derek M. Shore, Harel Weinstein
BIOPHYSICAL JOURNAL
(2020)