Article
Multidisciplinary Sciences
Brooke M. Britton, Remy A. Yovanno, Sara F. Costa, Joshua McCausland, Albert Y. Lau, Jie Xiao, Zach Hensel
Summary: In this study, the structure and dynamics of the E. coli divisome core complex were investigated using various techniques including structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. The interactions and roles of proteins FtsW, FtsI, FtsQ, FtsL, FtsB, and FtsN in the complex were explored. The findings provide insights into the mechanism of cell wall synthesis activation by FtsN through modulating interactions between FtsI and FtsW.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Joshua W. McCausland, Xinxing Yang, Georgia R. Squyres, Zhixin Lyu, Kevin E. Bruce, Melissa M. Lamanna, Bill Soderstrom, Ethan C. Garner, Malcolm E. Winkler, Jie Xiao, Jian Liu
Summary: The FtsZ protein is a key component in bacterial cell division, driving the movement of enzymes that synthesize septal peptidoglycan through treadmilling dynamics. This directional movement is dependent on the binding potential between FtsZ and the enzyme, as well as the balance between enzyme diffusion and FtsZ's treadmilling speed.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Mohamed Attaibi, Tanneke den Blaauwen
Summary: This review summarizes recent data on the regulation of septal peptidoglycan synthesis and proposes new structural models and interactions. It contributes to the understanding of bacterial fission and its regulatory mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Katie N. Kang, Joseph M. Boll
Summary: This study reveals a direct interaction between PBP1A and the divisome component PBP3 in Acinetobacter baumannii, highlighting the unique role of this enzyme in the division of this highly drug-resistant nosocomial pathogen.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhixin Lyu, Atsushi Yahashiri, Xinxing Yang, Joshua W. McCausland, Gabriela M. Kaus, Ryan McQuillen, David S. Weiss, Jie Xiao
Summary: Research has found that FtsN is part of the FtsWI sPG synthesis complex and its continuous movement is coupled with sPG synthesis, playing a crucial role in maintaining the activity of FtsWI synthesis.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Henri Voedts, Delphine Dorchene, Adam Lodge, Waldemar Vollmer, Michel Arthur, Jean-Emmanuel Hugonnet
Summary: Bacteria resist turgor pressure through peptidoglycan, with endopeptidases playing a crucial role in the synthesis of cell wall, facilitating the formation of different cross-linking structures.
Article
Microbiology
Xiaoyu Wang, Xueqin Ma, Zhe Li, Mingyue Niu, Meiting Zhai, Yaodong Chen
Summary: ZapAL is a novel FtsZ associated protein in Pseudomonas aeruginosa, which interacts with FtsZ and induces the formation of long straight double filaments. It has a mild effect on FtsZ's GTPase activity and stable assembly dynamics. Additionally, ZapAL may form heterodimers with ZapA and work together to stabilize the FtsZ protofilament and Z-ring structure.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Saidbakhrom Saidjalolov, Zainab Edoo, Matthieu Fonvielle, Louis Mayer, Laura Iannazzo, Michel Arthur, Melanie Etheve-Quelquejeu, Emmanuelle Braud
Summary: Carbapenems have been optimized to target Gram-negative bacteria producing extended-spectrum beta-lactamases for the treatment of tuberculosis. The introduction of substituents at position C2 has shown to increase drug efficacy. Synthesizing peptido-carbapenems with a phenethylthio substituent at C2 demonstrated improved activity compared to the reference drug meropenem.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Microbiology
Kristen Schroeder, Kristina Heinrich, Ines Neuwirth, Kristina Jonas
Summary: This study reveals the functional interaction between GroESL and the bacterial cell division machinery, with GroESL not only affecting peptidoglycan biosynthesis during cell division, but also influencing the dynamics of divisome assembly.
Article
Biology
Chidiebere Akusobi, Bouchra S. Benghomari, Junhao Zhu, Ian D. Wolf, Shreya Singhvi, Charles L. Dulberger, Thomas R. Ioerger, Eric J. Rubin, Bavesh D. Kana
Summary: This study identified essential genes in Mab and characterized the role of PBP-lipo in cell wall synthesis. Inhibition of PBP-lipo could increase the susceptibility of Mab to various antibiotics, making it a potential drug target for treating Mab infections.
Article
Biochemistry & Molecular Biology
Souvik Dey, Huan-Xiang Zhou
Summary: In this study, molecular dynamics simulations were used to reveal how the membrane anchor protein SepF in Mycobacterium tuberculosis binds to acidic membranes and stabilizes the interaction between the Z-ring and the membrane during bacterial cell division, leading to the recruitment of other membrane proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Bill Soderstrom, Matthew J. Pittorino, Daniel O. Daley, Iain G. Duggin
Summary: During infection, some uropathogenic Escherichia coli exhibit filamentation, a stress response that promotes bacterial dispersal and survival. This process involves dynamic repositioning of FtsZ division rings and the distribution of DamX protein throughout the cell envelope.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Rei Nakamoto, Sarp Bamyaci, Karin Blomqvist, Staffan Normark, Birgitta Henriques-Normark, Lok-To Sham
Summary: This study reveals a mechanism that coordinates the synthesis of capsular polysaccharides (CPS) and peptidoglycan in Streptococcus pneumoniae. CPS synthesis initiates from the division septum and propagates along the long axis of the cell, organized by the tyrosine kinase system CpsCD. The recruitment of CPS synthesis complex to the septum is mediated by proteins associated with the divisome.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Sonia Huecas, Lidia Araujo-Bazan, Federico M. Ruiz, Laura B. Ruiz-Avila, R. Fernando Martinez, Andrea Escobar-Pena, Marta Artola, Henar Vazquez-Villa, Mar Martin-Fontecha, Carlos Fernandez-Tornero, Maria L. Lopez-Rodriguez, Jose M. Andreu
Summary: Inhibition of bacterial division by targeting the key protein FtsZ is considered an attractive approach for discovering new antibiotics, but the lack of appropriate chemical tools has hindered the discovery of FtsZ antibacterial inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Cristina Velazquez-Suarez, Benjamin L. Springstein, Mercedes Nieves-Morion, Andreas O. Helbig, Ann-Katrin Kieninger, Iris Maldener, Dennis J. Nuernberg, Karina Stucken, Ignacio Luque, Tal Dagan, Antonia Herrero
Summary: Anabaena sp. PCC 7120 grows by forming filaments of communicating cells and SepT is a coiled-coil-rich protein located in the intercellular septa and cytoplasm of cells, playing an important role in cell division and the formation of bacterial multicellularity.
Article
Biochemistry & Molecular Biology
Thiago Seraphim, Nardin Nano, Yiu Wing Sunny Cheung, Siripat Aluksanasuwan, Carolina Colleti, Yu-Qian Mao, Vaibhav Bhandari, Gavin Young, Larissa Holl, Sadhna Phanse, Yuliya Gordiyenko, Daniel R. Southworth, Carol Robinson, Visith Thongboonkerd, Lisandra M. Gava, Julio C. Borges, Mohan Babu, Leandro R. S. Barbosa, Carlos H. Ramos, Philipp Kukura, Walid A. Houry
Summary: The R2TP complex, formed by RUVBL1 and RUVBL2 ATPases, associates with PIH1D1 and RPAP3 proteins and plays a role in promoting the formation of macromolecular complexes. RPAP3 is identified as the central subunit of R2TP, linking PIH1D1 and RUVBL1/2. The study provides insights into the structure and function of the R2TP complex.
Article
Biochemistry & Molecular Biology
Sang Hyun Lim, Jamie Snider, Liron Birimberg-Schwartz, Wan Ip, Joana C. Serralha, Hugo M. Botelho, Miqueias Lopes-Pacheco, Madalena C. Pinto, Mohamed Taha Moutaoufik, Mara Zilocchi, Onofrio Laselva, Mohsen Esmaeili, Max Kotlyar, Anna Lyakisheva, Priscilla Tang, Lucia Lopez Vazquez, Indira Akula, Farzaneh Aboualizadeh, Victoria Wong, Ingrid Grozavu, Teuta Opacak-Bernardi, Zhong Yao, Meg Mendoza, Mohan Babu, Igor Jurisica, Tanja Gonska, Christine E. Bear, Margarida D. Amaral, Igor Stagljar
Summary: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel that plays a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. This study used a high-throughput screening technique to map the protein-protein interactions of CFTR and identify potential drug targets for CF treatment. They discovered candidate proteins, such as FGL2, that may have significant effects on CFTR function in CF pathophysiology.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daniel R. Colman, Gilles Labesse, Gurla V. T. Swapna, Johanna Stefanakis, Gaetano T. Montelione, Eric S. Boyd, Catherine A. Royer
Summary: Dissimilatory sulfite reductase (DsrAB), an ancient enzyme, plays an important role in linking sulfur and carbon biogeochemical cycles. Through structural and evolutionary analyses, this study provides insights into the conservation of certain structural features in DsrAB and reveals potential allosteric communication pathways between subunits. These findings lay a foundation for future research on the biochemical and structural properties of DsrAB.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Virology
Subha Dahal, Ran Cheng, Peter K. Cheung, Terek Been, Ramy Malty, Melissa Geng, Sarah Manianis, Lulzim Shkreta, Shahrazad Jahanshahi, Johanne Toutant, Rose Chan, Sean Park, Mark A. Brockman, Mohan Babu, Samira Mubareka, Karen Mossman, Arinjay Banerjee, Scott Gray-Owen, Martha Brown, Walid A. Houry, Benoit Chabot, David Grierson, Alan Cochrane
Summary: In this study, the medicinal chemistry optimization of a known HIV-1 inhibitor led to the discovery of a new derivative, GPS491, which showed potent anti-HIV-1 activity with reduced toxicity. The study demonstrated that GPS491 not only blocked HIV-1 replication, but also inhibited the replication of adenovirus and multiple coronaviruses. Furthermore, GPS491 induced changes in viral RNA processing and altered the accumulation/phosphorylation/function of splicing regulatory SR proteins. This study highlights the potential of targeting cellular factors involved in RNA processing for the development of broad-spectrum antiviral agents.
Article
Neurosciences
Elisabet Jakova, Mohamed Taha Moutaoufik, Jeremy S. Lee, Mohan Babu, Francisco S. Cayabyab
Summary: This study found that adenosine and A1R receptor ligands interact with alpha-syn to modulate its aggregation and neurodegeneration. A1R agonists and drugs promoting a knot conformation of alpha-syn can cause alpha-synucleinopathy and increase neuronal degeneration, whereas A1R antagonists and drugs promoting a loop conformation of alpha-syn can be harnessed for possible neuroprotective therapies.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Cell Biology
Yuan Wang, Bochao Liu, Huimei Lu, Jingmei Liu, Peter J. Romanienko, Gaetano T. Montelione, Zhiyuan Shen
Summary: This study identifies a regulatory mechanism by which the cytoplasmic function of KU70 is enabled through methylation by SETD4. Mutations of SETD4 prevent methylation of KU70. The findings also reveal the importance of SETD4 and KU70K570 methylation in the suppression of apoptosis.
Article
Biochemistry & Molecular Biology
Yaohui Li, Rongzhen Zhang, Chi Wang, Farhad Forouhar, Oliver B. Clarke, Sergey Vorobiev, Shikha Singh, Gaetano T. Montelione, Thomas Szyperski, Yan Xu, John F. Hunt
Summary: The evolutionary benefit of oligomeric structures in proteins lacking evidence of intersubunit cooperativity is unclear. In this study, a conserved tetramer interface is shown to maintain the active-site structure in a certain class of proteins, the SDR superfamily. Oligomerization reduces the metabolic cost of enzyme biosynthesis and increases tolerance to destabilizing mutations, enhancing evolutionary fitness.
Article
Multidisciplinary Sciences
Casey M. Stevens, Svitlana O. Babii, Amitkumar N. Pandya, Wei Li, Yupeng Li, Jitender Mehla, Robyn Scott, Pooja Hegde, Pavan K. Prathipati, Atanu Acharya, Jinchan Liu, James C. Gumbart, Jeffrey North, Mary Jackson, Helen I. Zgurskaya
Summary: In this study, the researchers successfully purified and reconstituted MmpL3 and CmpL1 proteins into proteoliposomes. The proteins were found to facilitate proton translocation across a phospholipid bilayer, but they differed in their pH responses and interactions with substrate mimics and inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Alla Gagarinova, Ali Hosseinnia, Matineh Rahmatbakhsh, Zoe Istace, Sadhna Phanse, Mohamed Taha Moutaoufik, Mara Zilocchi, Qingzhou Zhang, Hiroyuki Aoki, Matthew Jessulat, Sunyoung Kim, Khaled A. Aly, Mohan Babu
Summary: By studying genetic interactions among all transcription factor genes in E. coli, this research reveals condition-dependent interactions and uncovers the roles of uncharacterized transcription factors.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Roberto Tejero, Yuanpeng Janet Huang, Theresa A. Ramelot, Gaetano T. Montelione
Summary: Recent advances in molecular modeling, particularly AlphaFold, have the potential to revolutionize structural biology, as it provides protein structure models with accuracies similar to or even better than experimental data. This holds promise for guiding the analysis of experimental data and has broader applications in the field.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Gaurav Bhardwaj, Jacob O'Connor, Stephen Rettie, Yen-Hua Huang, Theresa A. Ramelot, Vikram Khipple Mulligan, Gizem Gokce Alpkilic, Jonathan Palmer, Asim K. Bera, Matthew J. Bick, Maddalena Di Piazza, Xinting Li, Parisa Hosseinzadeh, Timothy W. Craven, Roberto Tejero, Anna Lauko, Ryan Choi, Calina Glynn, Linlin Dong, Robert Griffin, Wesley C. van Voorhis, Jose Rodriguez, Lance Stewart, Gaetano T. Montelione, David Craik, David Baker
Summary: This study investigates the design principles for macrocycle membrane permeability and oral bioavailability using computational design and experimental characterization. The results show that membrane permeability can be achieved by engaging all amide (NH) groups in internal hydrogen bonding interactions. Additionally, designs with exposed NH groups can be made membrane permeable through the design of an alternative isoenergetic fully hydrogen-bonded state favored in the lipid membrane. The ability to design membrane-permeable and orally bioavailable peptides with high structural accuracy has significant implications for the development of next-generation macrocycle therapeutics.
Article
Biochemical Research Methods
Keith J. Fraga, Yuanpeng J. Huang, Theresa A. Ramelot, G. V. T. Swapna, Arwin Lashawn Anak Kendary, Ethan Li, Ian Korf, Gaetano T. Montelione
Summary: NMR is a valuable experimental tool for structural biologists to study biomolecules. The progress of machine learning highlights the importance of large, diverse, and reliable datasets in structural biology. By organizing NMR data and using machine learning methods, long-standing problems in NMR data processing and structure determination can be tackled.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Zoology
Yaa Adarkwa Darko, Olaf Voss, Peter Uetz
Summary: Species are typically described using morphological terms, but there is currently no standardization for these terms and their abbreviations. Standardization is necessary for future machine-readability of all species descriptions in biology.
Article
Microbiology
Silvia Gervasoni, Jitender Mehla, Charles R. Bergen, Inga V. Leus, Enrico Margiotta, Giuliano Malloci, Andrea Bosin, Attilio V. Vargiu, Olga Lomovskaya, Valentin V. Rybenkov, Paolo Ruggerone, Helen I. Zgurskaya
Summary: This study investigated the dynamics of MexB interactions with its ligands using machine learning, computational and experimental approaches. The results showed that MexB ligands can be effectively expelled or hindered in the transporter cycle based on their interactions with specific residues in MexB binding sites. The findings indicate that MexB ligands fit into a substrate-inhibitor spectrum depending on their physico-chemical properties. This molecular-level information is important for the rational design of new inhibitors and antibiotics less susceptible to the efflux mechanism.
Article
Chemistry, Analytical
Premkumari Kumarathasan, Nazila Nazemof, Dalibor Breznan, Erica Blais, Hiroyuki Aoki, James Gomes, Renaud Vincent, Sadhna Phanse, Mohan Babu
Summary: This study evaluated the internalization and mitochondrial effects of silica nanoparticles (SiNPs) with different sizes and surface modifications. The findings suggest that physicochemical properties are determinants of SiNP exposure-related mitochondrial effects. Mitochondrial exposures combined with proteomic analysis can serve as a new approach in risk assessment, providing insights into related toxicity mechanisms.