Article
Biochemistry & Molecular Biology
Dafeng Liu, Cai Yuan, Chenyun Guo, Mingdong Huang, Donghai Lin
Summary: This study reported the crystal structure and functional mechanism of the CpsY protein in Mycobacterium tuberculosis. The researchers found that CpsY has conserved regions and spacer segments surrounding its catalytic cavity, and the residue R419 is strictly conserved in regulating its phosphotransferase activity. In addition, deletion of certain spacer segments drastically increased the enzyme activity of CpsY.
Article
Microbiology
Fermin Acosta, Miguel Martinez-Lirola, Pedro J. Sola-Campoy, Jon Sicilia, Teresa Guerra-Galan, Sandra R. Maus, Patricia Munoz, Laura Perez-Lago, Dario Garcia de Viedma
Summary: Genotyping tools are crucial for identifying the complexity of transmission clusters in Mycobacterium tuberculosis. This study analyzed the epidemiological and bacteriological complexity of a cluster in Almeria, Spain. The cluster, initially associated with Moroccan migrants, reappeared in Spanish-born individuals, with the identification of two clonal variants. The analysis involved whole-genome sequencing, epidemiological interviews, and characterization of isolates and specimens. The findings revealed the growing cluster with transmitted clonal diversity and amplified within-host diversity due to diagnostic delay. This study highlights the importance of a comprehensive approach in understanding the complexity of tuberculosis transmission events.
MICROBIOLOGY SPECTRUM
(2022)
Article
Chemistry, Multidisciplinary
Maria Voccia, Lukas Odenwald, Maximilian Baur, Fei Lin, Laura Falivene, Stefan Mecking, Lucia Caporaso
Summary: Polyethylene materials with in-chain-incorporated keto groups can be achieved by nonalternating copolymerization of ethylene with carbon monoxide using Ni(II) phosphinephenolate catalysts. The mechanism of this reaction involves the isomerization of an alkyl-olefin intermediate as the rate-determining step. The formation of non-alternating incorporation is influenced by ethylene binding, while the formation of alternating motifs is determined by the opening of the C,O-chelate. The crucial feature of these Ni(II) catalysts is the eta(2)-coordination of a P-bound aromatic moiety axially oriented to the metal center, which also affects the competition between the two pathways. The conformational constraints imposed in a 2',6'-dimethoxybiphenyl moiety result in disfavoring ethylene coordination along the alternating incorporation pathway, primarily governed by electronics, while not penalizing the nonalternating chain growth, primarily governed by sterics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Geochemistry & Geophysics
Xinxin Mo, Matthew G. Siebecker, Wenxian Gou, Wei Li
Summary: This study investigated the sorption mechanisms of nickel at palygorskite/solution interfaces using various techniques. The results showed different reaction kinetics at different pH conditions and the formation of different surface complexes or precipitates at different ionic strengths, shedding light on metal sequestration and surface precipitation phenomena at mineral/water interfaces.
GEOCHIMICA ET COSMOCHIMICA ACTA
(2021)
Article
Infectious Diseases
Ki-Young Lee, Bong-Jin Lee
Summary: Type II toxin-antitoxin (TA) modules are commonly found in prokaryotes and play roles in maintaining cell survival under adverse conditions. The antitoxins' intrinsically disordered regions (IDRs) have been shown to have helical conformations and function as central hubs in regulatory protein interaction networks. However, the biological and pathogenic functions of these IDRs are not well discussed compared to those in eukaryotic proteomes. This article focuses on the versatile roles of IDRs in type II antitoxins and provides insights into the discovery of new antibiotic candidates.
Article
Biochemistry & Molecular Biology
Amar Pratap Singh, Rakesh Kumar, Dinesh Gupta
Summary: Human PRMT4, also known as CARM1, is a type I arginine methyltransferase protein. Structural studies reveal the importance of the N-terminal region, Rossman fold, and dimerization arm in PRMT4 activity. Further elucidation is needed on the communication pathways in PRMT4. Molecular dynamics simulations and network analysis show differences in monomeric and dimeric forms of hPRMT4, as well as the existence of communication networks and an allosteric pathway. These findings provide insights into conformational changes, dimerization mechanism, SAM binding, and inhibitor design for hPRMT4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Inorganic & Nuclear
Venkadesh Balakrishnan, Vetrivelan Murugesan, Bincy Chindan, Ramesh Rasappan
Summary: In nickel-mediated Kumada cross-coupling reactions, the stability and reactivity of low valent active nickel complexes are determined by ligands. Recent studies have shown that AgF can reduce the decomposition of active nickel complexes, and both Ni(0) and Ni(I) have been identified as active species in these reactions.
INORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Tao Luo, Peng Xu, Yangyi Zhang, Jessica L. Porter, Marwan Ghanem, Qingyun Liu, Yuan Jiang, Jing Li, Qing Miao, Bijie Hu, Benjamin P. Howden, Janet A. M. Fyfe, Maria Globan, Wencong He, Ping He, Yiting Wang, Houming Liu, Howard E. Takiff, Yanlin Zhao, Xinchun Chen, Qichao Pan, Marcel A. Behr, Timothy P. Stinear, Qian Gao
Summary: A population genomics analysis of Mycobacterium kansasii reveals municipal water as a main source of infection and shows that nearly 80% of infections are due to closely-related strains, forming a main cluster that originated in the 1900s. Bioinformatic analyses suggest that certain genes may have contributed to the pathogen's success and adaptation to the human host.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Hemant Joshi, Divya Kandari, Rakesh Bhatnagar
Summary: Effective treatment of tuberculosis faces two hurdles: the establishment of persistent infections and the reactivation of persistent bacteria into active pathogens. Extensive research has been conducted to combat the drug resistance and immune evasion of Mycobacterium tuberculosis, a major public health concern. Recent advancements in understanding the mechanisms of persister cell formation have shed light on potential preventive or treatment measures.
Article
Immunology
Elisa Petruccioli, Linda Petrone, Teresa Chiacchio, Chiara Farroni, Gilda Cuzzi, Assunta Navarra, Valentina Vanini, Umberto Massafra, Marianna Lo Pizzo, Giuliana Guggino, Nadia Caccamo, Fabrizio Cantini, Fabrizio Palmieri, Delia Goletti
Summary: Patients with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have a higher risk of developing active tuberculosis (TB) compared to the general population. Studying the M. tuberculosis (Mtb) specific T-cell response may help identify immune biomarkers of Mtb burden or clearance in different TB statuses and risk groups.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Endocrinology & Metabolism
Brice Beinsteiner, Isabelle M. L. Billas, Dino Moras
Summary: Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor that plays a crucial role in regulating liver-specific gene expression. Dysregulation of HNF4 is associated with human diseases like type I diabetes and hemophilia. This review focuses on the structures of HNF4 and its impact on the receptor's structure-function relationship.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Microbiology
Cristina Parada, Isabel Cecilia Neri-Badillo, Antonio J. Vallecillo, Erika Segura, Mayra Silva-Miranda, Silvia Laura Guzman-Gutierrez, Paola A. Ortega, Enrique Wenceslao Coronado-Aceves, Laura Cancino-Villeda, Alfredo Torres-Larios, Michel de Jesus Aceves Sanchez, Mario Alberto Flores Valdez, Clara Espitia
Summary: The study highlights the importance of protein methylation in modulating immune response and fatty acid transport in Mycobacterium tuberculosis. This provides new insights into the pathogenesis of tuberculosis and underscores the significance of heterologous expression systems in obtaining modified proteins.
Review
Biochemistry & Molecular Biology
Jennifer Y. Cui, George P. Lisi
Summary: Cytokines play a key role in cellular communication and biological regulation. Their timing, quantity, and localization are crucial in producing specific biological outcomes. Through molecular observation, insights gained may complement a system-level understanding of cytokine biology, explaining the diversity of downstream signaling events and informing therapeutic and experimental development.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Microbiology
Mariana P. Lanfranconi, Ana Arabolaza, Hugo Gramajo, Hector M. Alvarez
Summary: The study conducted a comprehensive phylogenetic analysis to reveal the evolutionary divergence of HBHAMT in Mycobacterium tuberculosis, as well as the functional differentiation in the hbha gene cluster in slow-growing pathogenic mycobacteria. The heterologous expression of HBHAMT in oleaginous R. opacus PD630 provides insights into the protein binding to lipid droplets, similar to HBHA proteins found in saprophytic mycobacteria. The research proposes an evolutionary scenario to explain the structural and functional divergence of HBHA in fast and slow-growing mycobacteria.
ARCHIVES OF MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tanaya Basu Roy, Siddhartha P. Sarma
Summary: This study decodes the details of transcriptional autoregulation by the MazE9 antitoxin in the Mycobacterium tuberculosis MazEF9 toxin-antitoxin system. The researchers found that MazE9 specifically interacts with the mazEF9 operon and identified the thermodynamic and kinetic parameters of this interaction. The study also showed that MazE9 is unlikely to cross-regulate with the functionally related mazEF6 operon. Additionally, an interesting feature of MazE9 is the cis-trans conformational isomerization of proline residues in its intrinsically disordered C-terminal domain.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Andy Weiss, Caitlin C. Murdoch, Katherine A. Edmonds, Matthew R. Jordan, Andrew J. Monteith, Yasiru R. Perera, Aslin M. Rodriguez Nassif, Amber M. Petoletti, William N. Beavers, Matthew J. Munneke, Sydney L. Drury, Evan S. Krystofiak, Kishore Thalluri, Hongwei Wu, Angela R. S. Kruse, Richard D. DiMarchi, Richard M. Caprioli, Jeffrey M. Spraggins, Walter J. Chazin, David P. Giedroc, Eric P. Skaar
Summary: This study reveals the existence of a conserved COG0523 protein family in vertebrates and assigns them an important role in regulating cellular zinc homeostasis.
Article
Microbiology
Erin R. Green, Joseph N. Fakhoury, Andrew J. Monteith, Hualiang Pi, David P. Giedroc, Eric P. Skaar
Summary: This study reveals that Acinetobacter baumannii causes more virulent pneumonia following desiccation and identifies the genetic requirements for desiccation. The disruption of Lon protease enhances desiccation tolerance, while bacterial hydrophilins DtpA and DtpB play a crucial role in this process.
CELL HOST & MICROBE
(2022)
Article
Biochemistry & Molecular Biology
Yifan Zhang, Julia E. Martin, Katherine A. Edmonds, Malcolm E. Winkler, David P. Giedroc
Summary: The novel virulence associated Rrf2-family transcriptional repressor SifR regulates genes involved in iron uptake and stress response in Streptococcus pneumoniae, providing insight into how the bacterium acquires iron sources in the host environment. This study sheds light on the mechanisms by which the pathogen adapts to oxidative stress and utilizes catechol-derived iron sources for survival.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Gaurav Sharma, Kenneth M. Merz
Summary: Zinc is an essential transition metal ion that plays multiple roles in cellular function. This study used molecular dynamics simulations to explore the structure-function relationship of YiiP protein in a lipid bilayer and proposed a hypothesis on the zinc efflux mechanism. The study revealed the important role of zinc ions in restraining the protein's transmembrane domains and suggested the guiding role of amino acid H153 in transporting zinc ions. Understanding the zinc transport process can provide insights into treating diseases such as diabetes and cancer.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Biochemical Research Methods
Susanta Das, Kiyoto Aramis Tanemura, Laleh Dinpazhoh, Mithony Keng, Christina Schumm, Lydia Leahy, Carter K. Asef, Markace Rainey, Arthur S. Edison, Facundo M. Fernandez, Kenneth M. Merz
Summary: In this study, an efficient CCS computational workflow was developed to accurately predict unknown structures using a machine learning model and standard DFT methods. TWIMS experiments were performed to validate the experimental values and assess uncertainties. The workflow yielded accurate structural predictions and provided unique insights into preferred conformations.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemistry & Molecular Biology
Madushanka Manathunga, Andreas W. Gotz, Kenneth M. Merz
Summary: Quantum chemistry allows for the study of systems with high accuracy, but its computational expense limits its application to a few atoms. To optimize performance, methods such as implementing quantum mechanical methods on modern hardware and using multiscale approaches have been developed. Simplified QM methods, including the use of machine learning, have also been created to enhance the speed and accuracy of calculations.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Physical
Ali Rahnamoun, Kurt A. O'Hearn, Mehmet Cagri Kaymak, Zhen Li, Kenneth M. Merz, Hasan Metin Aktulga
Summary: A novel locally polarizable multisite model based on the original cation dummy atom (CDA) model is proposed for molecular dynamics simulations of ions in condensed phases. The model introduces polarization effects by the electronegativity equalization model (EEM) method, allowing charges on the metal ion and its dummy atoms to fluctuate in response to the environment. This model can be coupled with nonpolarizable or polarizable water models and enhances the original fixed charge CDA model by adapting to the local solvent structure.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Physical
Abhishek Thakur, Gaurav Sharma, Vishnu Nayak Badavath, Venkatesan Jayaprakash, Kenneth M. Merz, Galia Blum, Orlando Acevedo
Summary: The COVID-19 outbreak has caused massive devastation worldwide, with millions of infections and deaths reported. Using a combination of crystal structures and validated inhibitors, four rules for designing potent inhibitors of SARS-CoV-2 main protease have been proposed. Experimental examination identified a potential lead compound with higher potency than known inhibitors.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Editorial Material
Chemistry, Medicinal
Guo-Wei Wei, Feng Zhu, Kenneth M. Merz
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Brenna J. C. Walsh, Sofia Soares Costa, Katherine A. Edmonds, Jonathan C. Trinidad, Federico M. Issoglio, Jose A. Brito, David P. Giedroc
Summary: Hydrogen sulfide (H2S) is a cytoprotective agent used by bacteria in response to stress, and this study found that exogenous sulfide alters protein abundance and metabolic reactions in the gut microorganism Enterococcus faecalis, potentially affecting fatty acid pathways.
Article
Chemistry, Medicinal
Madushanka Manathunga, Hasan Metin Aktulga, Andreas W. Gotz, Jr Kenneth M. Merz
Summary: The researchers have ported and optimized the GPU-accelerated QUICK and AMBER-based QM/MM implementation on AMD GPUs. This includes the entire Fock matrix build and force calculation in QUICK, along with general performance improvements to the QUICK GPU code. Benchmark tests on NVIDIA V100 and AMD MI100 cards show similar performance for standalone HF/DFT calculations and QM/MM molecular dynamics simulations with QUICK and QUICK/AMBER. In addition, significant speedups are observed for QM/MM molecular dynamics simulations compared to the previous release version.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Editorial Material
Chemistry, Medicinal
Kenneth M. Merz, Guo-Wei Wei, Feng Zhu
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Zhen Li, Lin Frank Song, Gaurav Sharma, Basak Koca Findik, Kenneth M. Merz
Summary: Modeling the interaction between metal ions and small molecules is crucial in bridging the gap between two types of simulations. The 12-6-4 LJ nonbonded model has been successful in simulating metal ion systems and can accurately describe the three-component interactions by tuning the polarizability of the chelating atom. The transferability of this model has also been tested.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Physical
Hsu-Chun Tsai, Tai-Sung Lee, Abir Ganguly, Timothy J. Giese, Maximilian C. C. J. C. Ebert, Paul Labute, Kenneth M. Merz, Darrin M. York
Summary: We propose a framework for optimized alchemical transformation pathways in free energy simulations using nonlinear mixing and a new functional form for softcore potentials. The framework is implemented and tested in the GPU-accelerated AMBER software suite. The optimized pathways integrate important features such as smoothstep functions, power scaling of interactions, LJ pairwise form, and smoothing of the potential at the nonbonded cutoff boundary. The pathways demonstrate superior numerical stability and minimal variance of free energy estimates compared to traditional methods.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Madelyn Smith, Zhen Li, Luke Landry, Kenneth M. Merz, Pengfei Li
Summary: Atomic radii are important in scientific research and can be derived from crystal structures. However, determining the van der Waals (VDW) radii of ions is a challenge due to the combination of VDW and electrostatic interactions in crystal structures. In this study, VDW radii were determined based on a wavefunction analysis, showing excellent agreement with experimentally determined VDW radii of noble-gas atoms.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)