Article
Biochemistry & Molecular Biology
Wu Chengyong, Xian Jinghong, Wang Yanyan, Xiao Qing-Jie, Ma Lingling, Li Yuyan, Chen Hai, Lei Qian, Zhang Quan, Sun Bo, Wang Yuxi
Summary: This study investigated the interaction between tubulin vinca-domain ligands and tubulin, providing high-resolution crystal structures and revealing critical residues involved in the molecular mechanism. The designed novel triazolopyrimidine derivatives show potential for establishing new interactions with tubulin. This research lays the groundwork for developing innovative tubulin vinca-domain ligands.
Article
Biology
Andrea E. Prota, Daniel Lucena-Agell, Yuntao Ma, Juan Estevez-Gallego, Shuo Li, Katja Bargsten, Fernando Josa-Prado, Karl-Heinz Altmann, Natacha Gaillard, Shinji Kamimura, Tobias Muhlethaler, Federico Gago, Maria A. Oliva, Michel O. Steinmetz, Wei-Shuo Fang, J. Fernando Diaz
Summary: This study provides atomic-level details of the interaction between paclitaxel and tubulin, shedding light on the mechanism of action and binding determinants.
Article
Multidisciplinary Sciences
Ju Zhou, Anhui Wang, Yinlong Song, Nan Liu, Jia Wang, Yan Li, Xin Liang, Guohui Li, Huiying Chu, Hong-Wei Wang
Summary: In this study, the authors explore the enigma of GTP-triggered microtubule assembly. The proposed flexible model emphasizes longitudinal and lateral contacts, enhancing our understanding of microtubule nucleation and assembly.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Chongrong Shen, Shenghai Chang, Qinghua Luo, Kevin Chun Chan, Zhibo Zhang, Bingnan Luo, Teng Xie, Guangwen Lu, Xiaofeng Zhu, Xiawei Wei, Changjiang Dong, Ruhong Zhou, Xing Zhang, Xiaodi Tang, Haohao Dong
Summary: The outer membrane structure is found in various organisms and plays a crucial role in material exchange. OMPs, which are present in this structure, share a common evolutionary origin and folding mechanism. This study investigates the assembly process of OMPs, revealing the sequential conformational dynamics of BAM, along with the functional residues of BamA and EspP in barrel hybridization, closure, and release.
Article
Chemistry, Multidisciplinary
Min Sun, Congyu Wang, Mingchen Lv, Zhen Fan, Jianzhong Du
Summary: By utilizing enzymatic catalysis, we have successfully developed a new tripeptide that can self-assemble into nanoparticles inside cells, exhibiting excellent interference capability and ultimately reversing drug resistance in melanoma. The tripeptide assembly can interfere with the self-polymerization of microtubules, resulting in cell cycle arrest and mitochondrial dysfunction, eventually inducing apoptosis. In vivo experiments have demonstrated that the tripeptide treatment significantly reduces the tumor volume of drug-resistant melanoma.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Michael Adams, Rahul Sharma, Thomas Colby, Felix Weis, Ivan Matic, Sagar Bhogaraju
Summary: The study reveals that Legionella pneumophila suppresses the toxicity of SdeA and other effector proteins using SidJ, and provides insights into the mechanism of protein glutamylation.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Ushasi Pramanik, Atanu Nandy, Laxmikanta Khamari, Saptarshi Mukherjee
Summary: Intrinsically disordered proteins (IDPs) possess unique dynamic characteristics that are difficult to study using traditional methods. Single-molecule measurements provide a better understanding of the conformational transitions of IDPs. These approaches are important for revealing the structural transitions of IDPs and future research directions.
Article
Biochemistry & Molecular Biology
Wenting Li, Lun Tan, Zhixiong Zhang, Qiuqi Xia, Dongsheng Lei, Yuyan Li, Ting Zhang, Shaoxue Zeng, Xiutian Sima, Yanyan Wang
Summary: Microtubule-targeting agents (MTAs) are widely used anti-cancer drugs, with various inhibitors and antibody drug conjugates approved for clinical use. Recent research has focused on determining crystal structures of tubulysin analogues and providing insights for designing new vinca-site ligands. Novel design strategies for tubulysin analogues were proposed, aiming to inspire the development of new MTAs or payloads in cancer therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Jongju Lee, Alex D. Nikolov, Darsh Wasan
Summary: The research discusses the history and recent advances in the measurement and modeling of oscillatory structural forces (OSF), including the use of advanced techniques and Henderson's theory. It also proposes a method to extend the theory to model the layer and in-layer structural transition of a capillary system.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Physics, Multidisciplinary
Margaret R. McCarter, Kook Tae Kim, Vladimir A. Stoica, Sujit Das, Christoph Klewe, Elizabeth P. Donoway, David M. Burn, Padraic Shafer, Fanny Rodolakis, Mauro A. P. Goncalves, Fernando Gomez-Ortiz, Jorge Iniguez, Pablo Garcia-Fernandez, Javier Junquera, Stephen W. Lovesey, Gerrit van der Laan, Se Young Park, John W. Freeland, Lane W. Martin, Dong Ryeol Lee, Ramamoorthy Ramesh
Summary: An escalating challenge in condensed-matter research is the characterization of emergent order parameter nanostructures. Resonant elastic x-ray scattering (REXS) has emerged as a technique to study chirality in spin textures, but its application in ferroelectrics is limited. This study presents a framework for modeling REXS from an arbitrary arrangement of charge quadrupole moments and demonstrates its ability to probe the structure and chirality of polar skyrmions.
PHYSICAL REVIEW LETTERS
(2022)
Article
Chemistry, Medicinal
Jiao Li, Fumei Zhong, Mingwei Li, Yaqian Liu, Lei Wang, Mingqing Liu, Fudong Li, Jiahai Zhang, Jihui Wu, Yunyu Shi, Zhiyong Zhang, Xiaoming Tu, Ke Ruan, Jia Gao
Summary: This study elucidates the crystal structure of SARS-CoV-2 Mac3, identifies two small-molecule binding sites, and confirms the binding properties and functions of two drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Luke S. Ferro, Qianglin Fang, Lisa Eshun-Wilson, Jonathan Fernandes, Amanda Jack, Daniel P. Farrell, Mert Golcuk, Teun Huijben, Katelyn Costa, Mert Gur, Frank DiMaio, Eva Nogales, Ahmet Yildiz
Summary: Research has found that MAP7 is a required cofactor for kinesin-1-driven transport of intracellular cargoes. MAP7 binds to microtubules (MTs) and facilitates kinesin-1 motility, but it also inhibits kinesin-1 motility by partially overlapping with its binding site. However, by tethering kinesin-1 to the MT, MAP7 prevents dissociation of the motor and facilitates its binding to other available sites. This biphasic regulation of kinesin-1 by MAP7 becomes dominant when MTs are saturated with MAP7.
Article
Chemistry, Physical
N. M. Kleinerman, N. V. Mushnikov, A. V. Protasov, V. S. Gaviko, O. A. Golovnya, S. P. Naumov
Summary: The structure and magnetic state of Fe100-xNix alloys (x ≤ 20) quenched from 1100 degrees C were investigated using Mössbauer spectroscopy, X-ray diffraction, transmission electron microscopy, and magnetization measurements. The concentration dependences of the lattice parameter of bcc structure and the spontaneous magnetic moment at room temperature were measured. Mössbauer spectroscopy analysis revealed that both isomer shift and hyperfine field increased with increasing Ni content in the alloy. The structure of quenched Fe-Ni samples was found to consist of varying content bcc regions, formed as a result of separation of the alloy composition.
JOURNAL OF ALLOYS AND COMPOUNDS
(2023)
Article
Multidisciplinary Sciences
Menghang Huang, Xiaoxiao Zhang, Gee Ann Toh, Qin Gong, Jia Wang, Zhifu Han, Bin Wu, Franklin Zhong, Jijie Chai
Summary: The study demonstrates that full-length rat NLRP1 and rat DPP9 can form a complex to suppress NLRP1 activation. The ZU5 domain is essential for both autoinhibition of NLRP1 and assembly of the complex. Furthermore, both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells.
Article
Multidisciplinary Sciences
Shintaroh Kubo, Khanh Huy Bui
Summary: Intraflagellar transport in ciliary assembly and maintenance is driven by specific dynein and kinesins. Anterograde and retrograde transports occur on different regions of the microtubule. The regulatory mechanism of this selective process is not well understood. We simulated the motility of ciliary-specific dynein-2 under different post-translational modifications and found that poly-glutamylation can inhibit dynein-2 motility. This suggests that poly-glutamylation of the B-tubule can target retrograde transport onto the A-tubule.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Timothee Naret, Ilhem Khelifi, Olivier Provot, Jerome Bignon, Helene Levaique, Joelle Dubois, Martin Souce, Athena Kasselouri, Alain Deroussent, Angelo Paci, Paloma F. Varela, Benoit Gigant, Mouad Alami, Abdallah Hamze
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Heather C. Rice, Daniel de Malmazet, An Schreurs, Samuel Frere, Inge Van Molle, Alexander N. Volkov, Eline Creemers, Irena Vertkin, Julie Nys, Fanomezana M. Ranaivoson, Davide Comoletti, Jeffrey N. Savas, Han Remaut, Detlef Balschun, Keimpe D. Wierda, Inna Slutsky, Karl Farrow, Bart De Strooper, Joris de Wit
Article
Chemistry, Multidisciplinary
James P. Phelan, Simon B. Lang, Jaehoon Sim, Simon Berritt, Andrew J. Peat, Katelyn Billings, Lijun Fan, Gary A. Molander
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Chemistry, Applied
Steven M. Mennen, Carolina Alhambra, C. Liana Allen, Mario Barberis, Simon Berritt, Thomas A. Brandt, Andrew D. Campbell, Jesus Castanon, Alan H. Cherney, Melodie Christensen, David B. Damon, J. Eugenio de Diego, Susana Garcia-Cerrada, Pablo Garcia-Losada, Ruben Haro, Jacob Janey, David C. Leitch, Ling Li, Fangfan Liu, Paul C. Lobben, David W. C. MacMillan, Javier Magano, Emma McInturff, Sebastien Monfette, Ronald J. Post, Danielle Schultz, Barbara J. Sitter, Jason M. Stevens, Julia I. Strambeanu, Jack Twilton, Ke Wang, Matthew A. Zajac
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2019)
Article
Biochemistry & Molecular Biology
Fanomezana M. Ranaivoson, Liam S. Turk, Sinem Ozgul, Sumie Kakehi, Sventja von Daake, Nicole Lopez, Laura Trobiani, Antonella De Jaco, Natalia Denissova, Borries Demeler, Engin Ozkan, Gaetano T. Montelione, Davide Comoletti
Article
Chemistry, Multidisciplinary
Jisun Lee, Jason R. Schmink, Simon Berritt
JOURNAL OF CHEMICAL EDUCATION
(2020)
Article
Chemistry, Medicinal
Ekaterina S. Shchegravina, Elena Svirshchevskaya, Sebastien Combes, Diane Allegro, Pascale Barbier, Benoit Gigant, Paloma F. Varela, Andrei E. Gavryushin, Daria A. Kobanova, Andrey E. Shchekotikhin, Alexey Yu Fedorov
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Cell Biology
Rie Ayukawa, Seigo Iwata, Hiroshi Imai, Shinji Kamimura, Masahito Hayashi, Kien Xuan Ngo, Itsushi Minoura, Seiichi Uchimura, Tsukasa Makino, Mikako Shirouzu, Hideki Shigematsu, Ken Sekimoto, Benoit Gigant, Etsuko Muto
Summary: This study demonstrates that the formation of straight oligomers of critical size is essential for nucleation of microtubules. Both GDP and GTP tubulin form single-stranded oligomers with different curvature distributions, and the proportion of straight oligomers can accelerate nucleation. The results suggest that cellular factors involved in nucleation promote it via stabilization of straight oligomers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paloma F. Varela, Melanie Chenon, Christophe Velours, Kristen J. Verhey, Julie Menetrey, Benoit Gigant
Summary: Motile kinesins are motor proteins that move along microtubules by hydrolyzing ATP. This study provides structural insights into the nucleotide cycle of OSM-3, demonstrating a shared ATPase mechanism similar to that of Eg5 in the kinesin superfamily.
Article
Chemistry, Organic
Bowen Li, Bangke Luo, Caroline A. Blakemore, Aaron C. Smith, Daniel W. Widlicka, Simon Berritt, Wenjun Tang
Summary: A practical and efficient synthesis of alpha-heteroaryl propionic esters was achieved by employing palladium-catalyzed alpha-heteroarylation of silyl ketene acetals, forming a wide variety of esters with different substituents and functionalities in high yields. The success of this transformation can be attributed to the development of a bulky P,P=O ligand, providing an efficient synthesis of alpha-heteroaryl propionic acids.
Article
Multidisciplinary Sciences
Dafydd R. Owen, Charlotte M. N. Allerton, Annaliesa S. Anderson, Lisa Aschenbrenner, Melissa Avery, Simon Berritt, Britton Boras, Rhonda D. Cardin, Anthony Carlo, Karen J. Coffman, Alyssa Dantonio, Li Di, Heather Eng, RoseAnn Ferre, Ketan S. Gajiwala, Scott A. Gibson, Samantha E. Greasley, Brett L. Hurst, Eugene P. Kadar, Amit S. Kalgutkar, Jack C. Lee, Jisun Lee, Wei Liu, Stephen W. Mason, Stephen Noell, Jonathan J. Novak, R. Scott Obach, Kevin Ogilvie, Nandini C. Patel, Martin Pettersson, Devendra K. Rai, Matthew R. Reese, Matthew F. Sammons, Jean G. Sathish, Ravi Shankar P. Singh, Claire M. Steppan, Al E. Stewart, Jamison B. Tuttle, Lawrence Updyke, Patrick R. Verhoest, Liuqing Wei, Qingyi Yang, Yuao Zhu
Summary: PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor, has been discovered with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. This new drug has shown promise in countering the threat of COVID-19 with its oral activity and safety in clinical trials.
Article
Chemistry, Multidisciplinary
Andreas Stein, Persefoni Hilken Nee Thomopoulou, Corazon Frias, Sina M. Hopff, Paloma Varela, Nicola Wilke, Arul Mariappan, Jorg-Martin Neudoerfl, Alexey Yu Fedorov, Jay Gopalakrishnan, Benoit Gigant, Aram Prokop, Hans-Gunther Schmalz
Summary: The synthesis and investigation of PT-100, a potential anticancer drug, were reported. PT-100 exhibited high antiproliferative and apoptosis-inducing effects, especially in multidrug-resistant cancer cell lines, and showed synergistic effects with vincristine in certain cell lines.
Article
Multidisciplinary Sciences
Valerie Campanacci, Agathe Urvoas, Liza Ammar Khodja, Magali Aumont-Nicaise, Magali Noiray, Sylvie Lachkar, Patrick A. Curmi, Philippe Minard, Benoit Gigant
Summary: The study demonstrates the binding of CPAP's PN2-3 domain with tubulin and the similarity in binding mode with fungal and bacterial inhibitors. This finding uncovers the characteristic features of cellular partners binding to this site and highlights the structural convergence of CPAP with small-molecule inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Organic
Allyn T. Londregan, John M. Curto, Emma Hastry, Colin R. Rose, Simon Berritt
Summary: In this study, a general and convenient procedure for the synthesis of azinones is presented. Cyclopropylmethanol is used as a protecting group and surrogate for hydroxyl in various azines. The corresponding azinones can be formed and isolated in excellent yields after acidic deprotection under mild reaction conditions. More than 20 examples, along with reaction optimization, scope, and mechanism, are discussed.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Emma L. McInturff, Scott P. France, Carolyn A. Leverett, Andrew C. Flick, Erick A. Lindsey, Simon Berritt, Daniel W. Carney, Jacob C. DeForest, Hong X. Ding, Sarah J. Fink, Tony S. Gibson, Kaitlyn Gray, Aran K. Hubbell, Amber M. Johnson, Yiyang Liu, Subham Mahapatra, Indrawan J. McAlpine, Rebecca B. Watson, Christopher J. O'Donnell
Summary: New drugs introduced to the market each year provide valuable insights into molecular recognition and potential leads for future medicines. This annual review focuses on the process-scale synthetic approaches to 35 newly approved compounds worldwide in 2021, including small molecules and antibody-drug conjugates.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)