Article
Microbiology
Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Siriruk Changrob, Lei Li, Peter Halfmann, Nai-Ying Zheng, Henry Utset, Christopher T. Stamper, Haley L. Dugan, William D. Miller, Min Huang, Ya-Nan Dai, Christopher A. Nelson, Paige D. Hall, Maud Jansen, Kumaran Shanmugarajah, Jessica S. Donington, Florian Krammer, Daved H. Fremont, Andrzej Joachimiak, Yoshihiro Kawaoka, Vera Tesic, Maria Lucia Madariaga, Patrick C. Wilson
Summary: The study reveals that individuals with more severe SARS-CoV-2 infection have a stronger overall antibody response to the spike and nucleocapsid proteins, and a larger memory B cell response against the spike. Additionally, these individuals develop antibodies that cross-react with other viral antigens, suggesting potential protection against reinfection.
Article
Biochemistry & Molecular Biology
Vesna Stanojlovic, Anna Mueller, Ali Moazzam, Arthur Hinterholzer, Katarzyna Ozga, Lukasz Berlicki, Mario Schubert, Chiara Cabrele
Summary: The study introduces an acyclic but rigid β-hairpin scaffold XWXWXpPXK(/R)X(R) that exhibits high conformational stability, accommodating various side chains and showing versatility in accommodating different amino acid compositions.
Review
Chemistry, Inorganic & Nuclear
Stamatia Vassiliou, Aikaterini Pagoni, Ewelina Weglarz-Tomczak, Michal Talma, Wojciech Tabor, Agnieszka Grabowiecka, Lukasz Berlicki, Artur Mucha
Summary: The phosphinic acid functionality is a valuable scaffold for constructing biologically active compounds, particularly enzyme inhibitors. This article presents two recent achievements in using phosphinic acids as ligands for hydrolases, including the synthesis of a dipeptide analog inhibitor of metalloaminopeptidases and a catechol-based inhibitor of urease, as well as discussing the activity and mode of binding of phosphinic compounds to enzymes.
PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
(2022)
Article
Chemistry, Multidisciplinary
Monika Szefczyk, Katarzyna Ozga, Magda Drewniak-Switalska, Ewa Rudzinska-Szostak, Rafal Holubowicz, Andrzej Ozyhar, Lukasz Berlicki
Summary: The relationship between monomer structure and conformational properties at the oligomer level in foldamers remains a key issue in research. This study focused on the folding of peptidomimetic foldamers and factors affecting their conformational stability, specifically exploring the impact of peptide peripheral modification with trans- and cis-2-aminocyclopentanecarboxylic acid (ACPC) on the structure and stability of a model coiled-coil. The results showed significant differences in conformational stability between mutants containing trans-ACPC and cis-ACPC, despite differing only in one peripheral stereogenic center.
Article
Chemistry, Medicinal
Agnieszka Ciesiolkiewicz, Juan Lizandra Perez, Lukasz Berlicki
Summary: This review presents methodologies for the development of miniprotein scaffolds and the construction of biologically active miniproteins. It highlights the potential of miniproteins as drug candidates by virtue of their well-defined structure and good synthetic availability, particularly for targeting previously considered undruggable targets.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Multidisciplinary
Saurabh Loharch, Lukasz Berlicki
Summary: This review provides current knowledge on the structures, activity, and biological importance of bacterial ureases, and discusses the structure-based design of several classes of bacterial urease inhibitors. The study suggests that urease inhibitors may have potential therapeutic effects against Helicobacter pylori and Proteus spp. infections.
Article
Microbiology
Alfa Herrera, Youngchang Kim, Jiexi Chen, Robert Jedrzejczak, Shantanu Shukla, Natalia Maltseva, Grazyna Joachimiak, Lukas Welk, Grant Wiersum, Lukasz Jaroszewski, Adam Godzik, Andrzej Joachimiak, Karla J. F. Satchell
Summary: Alpha-pore-forming toxins (alpha-PFTs) are secreted by various bacteria and can form bi- or tripartite toxins, specifically targeting phagocytic cells.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Franz J. St John, Casey Crooks, Youngchang Kim, Kemin Tan, Andrzej Joachimiak
Summary: This report describes the first X-ray crystallographic structure models of a xylobiohydrolase (XBH) from Acetivibrio clariflavus, shedding light on the high functional specificity of this new bacterial GH30 XBH subfamily.
Review
Biochemistry & Molecular Biology
Marta Maslanka, Artur Mucha
Summary: Ebselen is a compound with low-molecular-weight that has been extensively researched due to its antioxidant, anti-inflammatory, and cytoprotective properties. Its inhibition of various enzymes and proteins attributes to its antimicrobial potential, with the covalent modification of cysteine residues being a key mechanism. This article summarizes the current understanding of Ebselen's antibacterial activity, both alone and in combination with commercial pharmaceuticals, and explores its molecular mechanism. The specific inactivation of certain enzymes, bacterial toxins, and resistance factors shows potential therapeutic implications. The synergistic effect and sensitization to common antibiotics when using Ebselen are promising directions for treating persistent infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Katarzyna Macegoniuk, Wojciech Tabor, Luca Mazzei, Michele Cianci, Miroslaw Giurg, Kamila Olech, Malgorzata Burda-Grabowska, Rafal Kaleta, Agnieszka Grabowiecka, Artur Mucha, Stefano Ciurli, Lukasz Berlicki
Summary: Screening of 25 analogs of Ebselen led to the discovery of highly potent inhibitors of Sporosarcina pasteurii urease, with a Ki value in a low picomolar range. The exceptional activity was attributed to the presence of a dihalogenated phenyl ring, which increased pi-pi and pi-cation interactions. Biological studies showed good potency for monosubstituted N-phenyl derivatives in inhibiting ureolysis in Proteus mirabilis cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Katarzyna Ozga, Lukasz Berlicki
Summary: An artificial retroaldolase was developed using a miniprotein derived from MvaT protein. Rational optimization of activity was performed by modifying the active motif, active site structure, and surface charge distribution, showing the potential for obtaining an effective enzyme-like catalyst and tuning its efficiency by optimizing surface charge distribution.
Article
Chemistry, Medicinal
Marta Maslanka, Wojciech Tabor, Pawel Krzyzek, Agnieszka Grabowiecka, Lukasz Berlicki, Artur Mucha
Summary: Catechols have been identified as potent covalent inhibitors of ureases by modifying cysteine residues at the active site. We synthesized novel catecholic derivatives with carboxylate and phosphonic/phosphinic groups, which demonstrated expanded specific interactions. The compound 2-(3,4-dihydroxyphenyl)-3-phosphonopropionic acid (15) exhibited significant anti-urease potential with a Ki value of 2.36 μM and displayed antiureolytic effects in live Helicobacter pylori cells at a submicromolar concentration (IC50 = 0.75 μM). Molecular modeling revealed its binding to the active site through electrostatic and hydrogen bond interactions. These catecholic phosphonic acids exhibited specific antiureolytic activity without cytotoxicity to eukaryotic cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wojciech Tabor, Aikaterini Katsogiannou, Danai Karta, Evgenia Andrianopoulou, Lukasz Berlicki, Stamatia Vassiliou, Agnieszka Grabowiecka
Summary: A series of thiourea-based urease inhibitors were synthesized and evaluated for their inhibitory activity against bacterial urease enzymes and whole cells. The inhibitors included diverse structural compounds such as thiosemicarbazones, thiocarbohydrazones, benzyl-substituted thiazolyl thioureas, 1H-pyrazole-1-carbothioamides, and dihydropirimidine-2(1H)-thiones. In kinetic studies, low micromolar inhibitors were identified within each structural group. Modeling studies showed the coordination of sulfur ions and hydrogen bonds in the active site of the enzymes. Whole-cell studies demonstrated the activity of these compounds against both Gram-positive and Gram-negative microorganisms. The inhibition of ureolysis in a pathogenic strain of P. mirabilis was particularly noteworthy.
Article
Chemistry, Physical
Monika Szefczyk, Natalia Szulc, Marlena Gasior-Glogowska, Dominika Bystranowska, Andrzej Zak, Andrzej Sikora, Oliwia Polanska, Andrzej Ozyhar, Lukasz Berlicki
Summary: In this paper, a hierarchical approach for constructing nanofibrils based on alpha,beta-peptide foldamers is proposed as a rational method for designing novel self-assembled nanomaterials. The incorporation of a specific amino acid residue resulted in the formation of helical foldamers, which was confirmed by spectroscopic techniques. The obtained alpha,beta-peptides showed a strong tendency to aggregate and form self-assembled nanostructures, as revealed by assays and microscopy. The location of the beta-amino acid in the coiled-coil structure affected the secondary structure and morphology of the self-assembled nanostructures.
Article
Biochemistry & Molecular Biology
Siva Santhiya Arul, Brinda Balakrishnan, Savithri S. Handanahal, Sangita Venkataraman
Summary: Viral nanoparticles are self-assembling delivery systems used for vaccines and therapeutic agents. They have improved biocompatibility and are widely used in various biomedical applications. However, large-scale production of VNPs still faces challenges.
Article
Biochemistry & Molecular Biology
Wisely Chua, Carl O. Marsh, Si En Poh, Winston LC. Koh, Melody Li Ying Lee, Li Fang Koh, Xin-Zi Emily Tang, Peter See, Zheng Ser, Shi Mei Wang, Radoslaw M. Sobota, Thomas L. Dawson Jr, Yik Weng Yew, Steven Thng, Anthony J. O'Donoghue, Hazel H. Oon, John E. Common, Hao Li
Summary: In this study, the gene expression of enzymes secreted by Malassezia globosa in the skin was investigated using targeted RNA sequencing. The study found that the expression of these enzymes is regulated by the fungus's environment and differs significantly from healthy skin sites. Additionally, a pseudoprotease MGL_3331 was identified to elicit an immune reaction in patients with atopic dermatitis. This highlights the importance of studying fungal proteins in physiologically relevant environments and their role in host immunity.
Article
Biochemistry & Molecular Biology
Belisa Parmeggiani, Marian Flores Signori, Cristiane Cecatto, Marina Rocha Frusciante, Manuela Bianchin Marcuzzo, Debora Guerini Souza, Rafael Teixeira Ribeiro, Bianca Seminotti, Diogo Onofre Gomes de Souza, Cesar Augusto Joa o Ribeiro, Moacir Wajner, Guilhian Leipnitz
Summary: Non ketotic hyperglycinemia (NKH) is a disorder caused by mutations in the genes encoding glycine cleavage system proteins, leading to severe neurodegeneration and white matter alterations. The study found that glycine affects myelin structure, glutamatergic system, and induces oxidative stress in neonatal rats and MO3.13 oligodendroglial cells.
Review
Biochemistry & Molecular Biology
Marie Rose Ndella Thiaw, Pascal Gantet
Summary: Mini zinc fingers play important roles in plant development, including control of cell division and expansion, meristem state transition, and growth and organ development. They have diverse modes of action, such as direct gene activation, interaction with specific transcription factors, and aggregation of protein complexes for chromatin remodeling. Further research is needed to explore their wider range of biological functions and their involvement in biotic and abiotic stress responses.
Article
Biochemistry & Molecular Biology
Shao-Jui Lai, Takahiro Kameda, Maasa Morita, Yuka Yamagata, Kaoruko Nishizaka, Yuna Horiuchi, Yukihiro Kobayashi, Yoko Usami, Jun-Jen Liu, Takeshi Kasama, Minoru Tozuka, Ryunosuke Ohkawa
Summary: In this study, the co-modification and impact of chymase and MPO on HDL were investigated. Sequential treatment with MPO and chymase generated two novel apoA-I fragments from HDL, one of which has a specific immunological property and can be used to predict patients with normal HDL-C levels and cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Xiao-Mi Sun, Asami Yoshida, Takuya Ishii, Yan-Rong Jiang, Yi-Li Gao, Mikinori Ueno, Katsuya Hirasaka, Kiyoshi Osatomi
Summary: This study found that infection with the causative bacteria of edwardsiellosis, Edwardsiella tarda NUF251, leads to the production of superoxide radicals, causing oxidative stress. The research on the Jfsod1 gene suggests that the transcription factor NF-IL6 plays a significant role in upregulating the transcriptional activity of the gene in response to oxidative stress induced by NUF251 infection.
Article
Biochemistry & Molecular Biology
Shane M. Carey, Sean P. Kearns, Matthew E. Millington, Gregory S. Buechner, Beda E. Alvarez Jr, Leily Daneshian, Brendan Abiskaroon, Maksymilian Chruszcz, Edward L. D'Antonio
Summary: The importance of F337 in TcGlcK was investigated using the hole mutagenesis approach, revealing its key interactions with aromatic tail groups in inhibitor molecules. Mutants retaining activity and structural similarity were obtained, suggesting the possibility of TcHxK existing as a monomer lacking the F337 residue. Similar D-glucosamine inhibitors may bind less strongly to TcHxK due to the absence of van der Waals contacts from residue side chains.
Article
Biochemistry & Molecular Biology
Catia Barria, Diogo Athayde, Guillem Hernandez, Leonor Fonseca, Jorge Casinhas, Tiago N. Cordeiro, Margarida Archer, Cecilia M. Arraiano, Jose A. Brito, Rute G. Matos
Summary: Ribonucleases play a crucial role in RNA regulation by processing, degrading, and quality controlling cellular transcripts. Campylobacter jejuni, the main cause of human gastroenteritis, relies on the exoribonuclease PNPase (CjPNP) for low-temperature survival, virulence factor synthesis, and swimming, cell adhesion/invasion, and chick colonization abilities. The crystallographic structure of CjPNP, along with SAXS analysis, confirms its trimeric arrangement and provides insight into domain arrangement and flexibility. Mutations in highly conserved residues reveal unexpected RNA degradation activity even under conditions favoring polymerization. These findings have significant implications for the development of strategies to combat C. jejuni infections.
Article
Biochemistry & Molecular Biology
Elvira R. Shaykhutdinova, Maria S. Severyukhina, Inna V. Kholoshenko, Elena A. Gondarenko, Irina V. Shelukhina, Elena V. Kryukova, Alina M. Ismailova, Elena S. Sadovnikova, Igor A. Dyachenko, Arkady N. Murashev, Victor I. Tsetlin, Yuri N. Utkin
Summary: Evidence suggests that activating nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury caused by ischemia and reperfusion. In this study, the expression of a4, a6, and a132 nAChR subunits in the rat heart's left ventricle was demonstrated. The nAChR agonists cytisine and varenicline, commonly used for nicotine addiction treatment, were found to significantly reduce myocardial ischemia-reperfusion injury, with varenicline showing greater protection. The presence of a4132, a7, and/or a6132-containing receptors suggests that the protective effect of varenicline may be mediated by these subunits. These findings indicate a potential new use for cytisine and varenicline as cardioprotective agents.
Article
Biochemistry & Molecular Biology
Xinhai Xiong, Wenjie Chen, Cheng Chen, Qi Wu, Chaopeng He
Summary: This article summarizes the important roles of Cx43 in disease development from the perspective of subcellular localization and provides new ideas for Cx43 as a therapeutic target and the search for related pathological mechanisms.
Article
Biochemistry & Molecular Biology
Veronica Bastos, Simone Pascoal, Kamila Lopes, Marcia Mortari, Helena Oliveira
Summary: Cancer, especially melanoma, is a major global health problem due to its metastatic capacity, treatment resistance, and high mortality rates. The Chartergellus-CP1 peptide isolated from Chartergellus communis wasp venom showed selective cytotoxicity towards melanoma cell lines, inducing apoptosis, cell cycle impairment, and intracellular ROS increase.
Article
Biochemistry & Molecular Biology
Charlotte Claeyssen, Nathan Bulangalire, Bruno Bastide, Onnik Agbulut, Caroline Cieniewski-Bernard
Summary: Maintenance of striated muscle tissue relies on a dynamic network of protein-protein interactions. Desmin intermediate filaments play a crucial role in heart and skeletal muscle by maintaining cell structure and contributing to various cellular processes. The assembly of desmin intermediate filaments requires aB-crystallin, which is involved in multiple cellular functions.
Article
Biochemistry & Molecular Biology
Dhritiman Dey, Adhiraj Dasgupta, Dipanjan Ghosh, Oindrila Bhattacharjee, Abhrajyoti Ghosh, Ayae Honda, Dhrubajyoti Chattopadhyay
Summary: This study successfully identified host factors that interact with Chandipura Virus (CHPV) and play a critical role in infection, including A2M, LRP1, and GRP78. Knocking out A2M has a severe effect on viral infection, indicating the potential role of these host proteins in viral entry into host cells.
Article
Biochemistry & Molecular Biology
Anna Dotsenko, Igor Sinelnikov, Aleksandra Rozhkova, Ivan Zorov, Arkady Sinitsyn
Summary: Xylanases play important roles in various industrial applications, such as feed additives, pulp and paper bleaching, and the production of bread, food, and drinks. Xylanases from the GH10 family show high thermostability and resistance to protein inhibitors, making them promising candidates for these processes. This study successfully improved the thermostability and enzymatic activity of GH10 xylanase, which could enhance its effectiveness as a feed additive and during pulp and paper bleaching.
Article
Biochemistry & Molecular Biology
M. Jaquet, M. Bengue, K. Lambert, G. Carnac, D. Misse, C. Bisbal
Summary: Changes to our environment have led to the emergence of human pathogens such as chikungunya virus, which is now a major public health concern. In this study, the interconnection between skeletal muscle cells metabolism, their differentiation stage, and the infectivity of chikungunya virus was investigated. The results showed that chikungunya virus infectivity is dependent on cell differentiation and metabolism and that the virus interferes with cellular metabolism.