Article
Multidisciplinary Sciences
Peter J. Mullen, Gustavo Garcia, Arunima Purkayastha, Nedas Matulionis, Ernst W. Schmid, Milica Momcilovic, Chandani Sen, Justin Langerman, Arunachalam Ramaiah, David B. Shackelford, Robert Damoiseaux, Samuel W. French, Kathrin Plath, Brigitte N. Gomperts, Vaithilingaraja Arumugaswami, Heather R. Christofk
Summary: This study revealed that SARS-CoV-2 infection alters host cell metabolism by increasing glucose entry into the TCA cycle and reducing oxidative glutamine metabolism. Additionally, infection with SARS-CoV-2 activates mTORC1, and inhibiting mTORC1 can suppress viral replication in kidney epithelial cells and lung ALI cultures. These findings suggest that targeting mTORC1 could be a potential treatment strategy for COVID-19 patients.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
George W. Roberts, David Leys
Summary: The ubiquitous UbiX-UbiD system is associated with a wide range of microbial (de)carboxylation reactions. Recent X-ray crystallographic studies have contributed to elucidating the enigmatic mechanism underpinning the conversion of alpha,beta-unsaturated acids by this system. The UbiD component utilises a unique cofactor, prenylated flavin (prFMN), generated by the bespoke action of the associated UbiX flavin prenyltransferase. Structure determination of a range of UbiX/UbiD representatives has revealed a generic mode of action for both the flavin-to-prFMN metamorphosis and the (de)carboxylation. In contrast to the conserved UbiX, the UbiD superfamily is associated with a versatile substrate range.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tek Narsingh Malla, Kara Zielinski, Luis Aldama, Sasa Bajt, Denisse Feliz, Brendon Hayes, Mark Hunter, Christopher Kupitz, Stella Lisova, Juraj Knoska, Jose Manuel Martin-Garcia, Valerio Mariani, Suraj Pandey, Ishwor Poudyal, Raymond G. Sierra, Alexandra Tolstikova, Oleksandr Yefanov, Chung Hong Yoon, Abbas Ourmazd, Petra Fromme, Peter Schwander, Anton Barty, Henry N. Chapman, Emina A. Stojkovic, Alexander Batyuk, Sebastien Boutet, George N. Phillips, Lois Pollack, Marius Schmidt
Summary: This study used mix-and-inject serial crystallography to trace atomic positions and elucidate essential enzymatic functions at the atomic level. The results reveal detailed information about ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection from the same set of data, providing insights into the inhibition of Mycobacterium tuberculosis enzyme by sulbactam.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Hui-Qing Yang, Ya-Ning Hou, Jing-Yun Chen, Sheng-Qiang Guo, Hui-Xian Yang, Xin Wang
Summary: We investigated the mechanism of asymmetric reductive carboxylation of N-(2-bromophenyl)-N-methylmethacrylamide catalyzed by a nickel complex using DFT calculations. The reaction proceeds via a multistep and elaborate mechanism, with CO2 showing a preference for inserting into the Ni(I) intermediate.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Xinmei Wang, Lu Qi, Lei Wu, Ruixin Zhang, Maierhaba Abudoureheman, Jiarong Lv, Peng Wang, Xiaoyu Dong, Qun Jing, Zhaohui Chen
Summary: Three non-centrosymmetric alkaline earth vanadyl(IV) phosphate hydrates (M(VO)(2)(PO4)(2)·4H(2)O, M = Ca, Sr, Ba) were successfully synthesized using a mild hydrothermal technique. The large birefringence of these compounds, calculated from first principles, is mainly attributed to the parallel arrangement of the (2)[V2P2O14](infinity) layers and the force of hydrogen bonds. Furthermore, the optical and thermal properties of these compounds were studied, providing insights for exploring nonlinear optical materials with large birefringence in vanadyl phosphate hydrates.
Review
Immunology
Shuo Ning, Beiming Yu, Yanfeng Wang, Feng Wang
Summary: This article provides a detailed description of the transmission mechanism and viral structure of the novel coronavirus, along with an analysis of potential therapeutic methods and effective chemical molecules and neutralizing antibodies that could help in the treatment of COVID-19.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Mikolaj Zmudzinski, Wioletta Rut, Kamila Olech, Jaroslaw Granda, Miroslaw Giurg, Malgorzata Burda-Grabowska, Rafal Kaleta, Michala Zgarbova, Renata Kasprzyk, Linlin Zhang, Xinyuanyuan Sun, Zongyang Lv, Digant Nayak, Malgorzata Kesik-Brodacka, Shaun K. Olsen, Jan Weber, Rolf Hilgenfeld, Jacek Jemielity, Marcin Drag
Summary: Proteases encoded by SARS-CoV-2, including the main protease (M-pro, 3CL(pro)) and papain-like protease (PLpro), are potential targets for new therapies against COVID-19. Ebselen, an organoselenium anti-inflammatory drug, has been shown to effectively inhibit these proteases and has been evaluated for its antiviral activity. This study screened a collection of ebselen derivatives for inhibitors against SARS-CoV-2 PLpro and M-pro and identified several compounds that are superior to ebselen. Additionally, ebselen was found to inhibit the N7-methyltransferase activity of SARS-CoV-2 nsp14 protein involved in viral RNA cap modification.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Wojciech K. Jankiewicz, Scott D. Barnett, Anna Stavniichuk, Sung Hee Hwang, Bruce D. Hammock, Jawad B. Belayet, A. H. Khan, John D. Imig
Summary: The study found that the dual sEH/COX-2 inhibitor PTUPB can alleviate hypertension and proteinuria induced by antiangiogenic therapy, and it has a protective effect on kidney tissue and function.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Juan Zhang, Fang-Yu Yang, Qi-Meng Zhu, Wen-Hao Zhang, Min Zhang, Jing Yi, Yan Wang, Hou-Li Zhang, Guo-Biao Liang, Jian-Kun Yan, Cheng-Peng Sun
Summary: A new sesquiterpenoid inulajaponoid A with anti-inflammatory effect was isolated from Inula japonica, which could serve as a potential target of soluble epoxide hydrolase (sEH).
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Sarah Barelier, Romain Avellan, Giri Raj Gnawali, Patrick Fourquet, Veronique Roig-Zamboni, Isabelle Poncin, Vanessa Point, Yves Bourne, Stephane Audebert, Luc Camoin, Christopher D. Spilling, Stephane Canaan, Jean-Francois Cavalier, Gerlind Sulzenbacher
Summary: We report the synthesis of new CyC alkyne-containing inhibitors (CyCyne) and their use for the direct fishing of target proteins in M. tb culture via bio-orthogonal click-chemistry activity-based protein profiling (CC-ABPP). This approach led to the capture and identification of a variety of enzymes, including HsaD, which is required for the survival of M. tb within macrophages and is a potential therapeutic target. The specificity of HsaD inhibition by the CyC analogues was confirmed through biochemical and structural approaches.
Article
Meteorology & Atmospheric Sciences
Zhaolu Hou, Jianping Li, Lei Wang, Yazhou Zhang, Ting Liu
Summary: The local dynamical analog (LDA) method is applied to correct the operational T2m forecast product in this study. By using spatially adjacent grids as analog pools, the T2m forecast in East Asia for December 2018 is improved. The root mean square error is reduced by 2%-4% and the correlation coefficient is increased by 1%-5% compared to ERA5 and station observation data.
ATMOSPHERIC RESEARCH
(2022)
Article
Multidisciplinary Sciences
Gabriela Dias Noske, Yun Song, Rafaela Sachetto Fernandes, Rod Chalk, Haitem Elmassoudi, Lizbe Koekemoer, C. David J. Owen, Tarick V. El-Baba, Carol Robinson, Glaucius Oliva, Andre Schutzer Godoy
Summary: The main protease of SARS-CoV-2, M-pro, is responsible for cleaving the viral polyprotein and is crucial for enzyme dimerization and activity. N-terminal cleavage is not critical for dimerization, and different types of inhibitors can affect the oligomeric states. This study provides insights into the maturation process of M-pro and how it can be targeted by inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Kang Liu, Ganghai Ni, Tao Luo, Junwei Fu, Hongmei Li, Min Liu, Zhang Lin
Summary: Single-atom M-N-2 (M=Fe, Co, Ni) catalysts exhibit high activity for CO2 reduction reaction. Using density functional theory calculations, this study reveals intermediates-induced CO2RR activity at the single-atom M-N-2 sites. Intermediates become part of the active moiety to optimize the adsorption of intermediates on the M sites. This work provides new insights into the understanding of the activity of single-atom M-N-2 sites.
Article
Chemistry, Physical
Xueying Luo, Xiaowei Wang, Yuan Yao, Xin Gao, Lu Zhang
Summary: This study has elucidated the template-dependent inhibitory mechanism of remdesivir on SARS-CoV-2 RdRp and identified the molecular mechanism of drug resistance caused by the V557L mutation.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Yacoba V. T. Minnow, Kajitha Suthagar, Keith Clinch, Rodrigo G. Ducati, Agnidipta Ghosh, Joshua N. Buckler, Rajesh K. Harijan, Sean M. Cahill, Peter C. Tyler, Vern L. Schramm
Summary: Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT) is an essential enzyme for the salvage pathway of hypoxanthine into parasite purine nucleotides. In this study, transition state analogue inhibitors of PfHGXPRT were characterized using kinetic analysis, thermodynamic parameters, and X-ray crystal structures. Compound 1, which is an acyclic ribocation phosphonate mimic linked to 9-deazaguanine, showed a kinetic Ki of 0.5 nM. Isothermal titration calorimetry experiments revealed enthalpically driven binding of compound 1 to PfHGXPRT with negative cooperativity. Crystal structures of the inhibitor bound to the enzyme provided insights into the hydrogen bond and ionic contacts involved in the binding process. The dynamics of ribosyl transfer from 5-phospho-alpha-D-ribosyl 1-pyrophosphate (PRPP) to hypoxanthine were investigated using 18O isotope exchange, which showed that rotational constraints and short transition state lifetimes prevented positional isotope exchange. The thermodynamic analysis of the transition state analogue and magnesium pyrophosphate binding indicated random and cooperative binding to PfHGXPRT, suggesting a different mechanism from the previously reported substrate kinetics.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Erin E. Price, Jeffrey M. Boyd
TRENDS IN MICROBIOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Viktor Dubovoy, Shiri Nawrocki, Gaurav Verma, Lukasz Wojtas, Primit Desai, Hassan Al-Tameemi, Tatiana Brinzari, Michael Stranick, Dailin Chen, Shaopeng Xu, Shengqian Ma, Jeffrey M. Boyd, Tewodros Asefa, Long Pan
Article
Biochemistry & Molecular Biology
Hassan Al-Tameemi, William N. Beavers, Javiera Norambuena, Eric P. Skaar, Jeffrey M. Boyd
Summary: S. aureus USA300 isolates utilize copBL and copAZ gene products to prevent Cu intoxication. A mutant strain lacking copAZ and copBL was sensitive to Cu and accumulated intracellular Cu. Mutations in the mntABC operon permitted growth in the presence of Cu, with transposon insertions in mntA being recessive. Defective MntABC resulted in decreased cellular Cu accumulation and protection to FeS enzymes from Cu poisoning.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Erin E. Price, Paulami Rudra, Javiera Norambuena, Franklin Roman-Rodriguez, Jeffrey M. Boyd
Summary: Transcriptional reporters are essential tools for studying gene regulation, and in this study, new vectors were developed for markerless insertion of codon-optimized lacZ-based reporters in Staphylococcus aureus. These vectors allow tailored lacZ expression with different ribosomal binding sites. The deletion of crtM gene allows for blue-white screening without interference from carotenoid production, and the methods described are compatible for monitoring transcriptional activity in anaerobic cultures. The study provides important insights into gene regulation in low-oxygen environments for S. aureus, a key human pathogen.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Microbiology
Edgar Ferrer-Gonzalez, Hyun Huh, Hassan M. Al-Tameemi, Jeffrey M. Boyd, Sang-Hyuk Lee, Daniel S. Pilch
Summary: This study investigates the synergistic effect of combination treatment with an FtsZ inhibitor and beta-lactam antibiotics on MRSA. The results suggest that PBP2, PBP4, and PBP2a may function collaboratively in peripheral cell wall repair in response to FtsZ inhibition. Understanding these mechanisms can help guide the development of effective drug regimens to combat MRSA infection and reduce resistance.
JOURNAL OF BACTERIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Erin E. Price, Franklin Roman-Rodriguez, Jeffrey M. Boyd
Summary: Bacterial respiration of diverse substrates is a key contributor to life diversity, driving changes in the geosphere and connecting ecological nodes. Organisms utilize respiration to dissipate reductants and generate energy, with mechanisms evolved to sense and regulate the utilization of respiration substrates for cellular health.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Gyu-Lee Kim, Thomas A. Hooven, Javiera Norambuena, Barry Li, Jeffrey M. Boyd, Jason H. Yang, Dane Parker
Summary: Studying the genetic elements of Staphylococcus aureus in pneumonia revealed that metabolic genes are crucial for lung infection, with growth and resistance to host defenses being key metabolic dimensions. This highlights the critical role of bacterial metabolism in surviving against host defenses during infection.
Article
Chemistry, Medicinal
Jimmy S. Patel, Javiera Norambuena, Hassan Al-Tameemi, Yong-Mo Ahn, Alexander L. Perryman, Xin Wang, Samer S. Daher, James Occi, Riccardo Russo, Steven Park, Matthew Zimmerman, Hsin-Pin Ho, David S. Perlin, Veronique Dartois, Sean Ekins, Pradeep Kumar, Nancy Connell, Jeffrey M. Boyd, Joel S. Freundlich
Summary: The study applied Bayesian modeling to identify chemical tools and drug discovery entities for drug-resistant Staphylococcus aureus infections, leading to the discovery of the active quinoline JSF-3151 and investigation of its intrabacterial transformation mechanism. Resistance mechanisms involving increased expression of a lipocalin protein and loss of function of an azoreductase in S. aureus were identified and validated, offering insights for developing therapeutic regimens for drug-resistant S. aureus.
ACS INFECTIOUS DISEASES
(2021)
Review
Microbiology
Karla Esquilin-Lebron, Sarah Dubrac, Frederic Barras, Jeffrey M. Boyd
Summary: Building iron-sulfur clusters and assembling Fe-S proteins are crucial for sustaining life, with genes coding for these proteins found in almost every sequenced genome. Defective assembly of Fe-S proteins can lead to cell death or metabolic defects.
Article
Chemistry, Multidisciplinary
Baran Teoman, Zilma Pereira Muneeswaran, Gaurav Verma, Dailin Chen, Tatiana Brinzari, Allison Almeda-Ahmadi, Javiera Norambuena, Shaopeng Xu, Shengqian Ma, Jeffrey M. Boyd, Piero M. Armenante, Andrei Potanin, Long Pan, Tewodros Asefa, Viktor Dubovoy
Summary: The compound CPC-Sn, consisting of cetylpyridinium chloride and stannous chloride, was synthesized and characterized with single-crystal X-ray diffraction, revealing a 1:1 ratio of cetylpyridinium cation and [SnCl3](-) anion. It has potential applications as a broad-spectrum antimicrobial agent and for producing advanced functional materials. Electrical resistance tomography showed that CPC-Sn has extended-release properties in aqueous environments compared to CPC.
Article
Microbiology
Taylor P. Andrews, J. Steen Hoyer, Nicole L. Fahrenfeld, Jeffrey M. Boyd, Siobain Duffy
Summary: This study presents the annotated whole-genome sequences of five cultured phietaviruses infecting Staphylococcus aureus, which are closely related to previously sequenced prophages in S. aureus genomes.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2022)
Article
Chemistry, Multidisciplinary
Jesse D. Hudspeth, Amy E. Boncella, Emily T. Sabo, Taylor Andrews, Jeffrey M. Boyd, Christine N. Morrison
Summary: In this work, the authors characterized two essential proteins involved in iron-sulfur cluster biogenesis in Staphylococcus aureus. They showed that these proteins are important in Gram-positive bacteria and focused on their potential as therapeutic targets for treating S. aureus infections. The authors provided a detailed characterization of the proteins and compared their activity to that of a related protein from Bacillus subtilis. Their results provide a basis for further investigation and the development of new treatment strategies.
Article
Nanoscience & Nanotechnology
Maricely Ramirez-Hernandez, Javiera Norambuena, Hongnan Hu, Belvin Thomas, Chaoyun Tang, Jeffrey M. Boyd, Tewodros Asefa
Summary: The urgent need for materials that can more efficiently deliver antimicrobial agents has arisen due to the increase in microbial resistance to traditional antibiotics. This study presents the synthesis of amine-functionalized SBA-15 mesoporous silica nanomaterials loaded with rafoxanide and anchored Cu(II) ions, which exhibit enhanced antimicrobial efficacy against pathogenic Staphylococcus aureus. The structurally characterized nanomaterials demonstrate 10 times the bactericidal action compared to nanomaterials loaded with rafoxanide only, and the synthetic sequence used in the production significantly impacts their bactericidal efficacy.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Microbiology
Javiera Norambuena, Hassan Al-Tameemi, Hannah Bovermann, Jisun Kim, William N. Beavers, Eric P. Skaar, Dane Parker, Jeffrey M. Boyd
Summary: Through metabolomic analyses, it was found that Cu ions can affect the growth and survival of S. aureus by inhibiting phosphoribosyl pyrophosphate synthetase (Prs). Experimental evidence demonstrated that Cu ions can inhibit the activity of Prs and lead to a decrease in intracellular PRPP levels. In mouse models, S. aureus that cannot effectively remove intracellular Cu ions lose the ability to colonize tissues.
Article
Microbiology
Taylor Andrews, J. Steen Hoyer, Karolyn Ficken, Paul D. Fey, Siobain Duffy, Jeffrey M. Boyd
Summary: This study reports the discovery of a culturable bacteriophage infecting Staphylococcus epidermidis, which belongs to a rapidly growing novel siphovirus genus. The identification of phages infecting S. epidermidis contributes to the development of phage therapy and the expansion of genome-based phage phylogeny.