Article
Biochemistry & Molecular Biology
Nubia Prates Toman, Anna Sophia Kamenik, Lucianna Helene Santos, Florian Hofer, Klaus R. Liedl, Rafaela Salgado Ferreira
Summary: This study utilized molecular dynamics simulations to investigate the selectivity in inhibition of cruzain or cathepsin L by chagasin mutants W93A, T31A, and T31A/T32A, revealing differences in binding modes and preferences of different mutants, providing insights into their impact on the activities of different enzymes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Medicine, Research & Experimental
Alexander Chan, Hejia Henry Wang, Rebecca M. Haley, Cindy Song, David Gonzalez-Martinez, Lukasz Bugaj, Michael J. Mitchell, Andrew Tsourkas
Summary: This study demonstrates the feasibility of using small protein scaffolds with anionic polypeptides to interact with positively charged nonviral lipid-based delivery systems, enabling efficient intracellular delivery. This method can be used to inhibit intracellular proteins that are currently not amenable to small molecule drugs and biologics.
MOLECULAR PHARMACEUTICS
(2022)
Article
Microbiology
Ethan C. Ashby, Jennifer L. Havens, Lindsey M. Rollosson, Johanna Hardin, Danae Schulz
Summary: African trypanosomiasis is a burdensome disease in sub-Saharan Africa, transmitted by a parasite through the tsetse fly. Chemical inhibition of bromodomain proteins causes significant changes in the transcriptome of both insect-stage and bloodstream-stage parasites. Understanding the gene-regulatory processes in these highly diverged eukaryotes may provide insights into the evolution of gene-regulatory mechanisms.
MICROBIOLOGY SPECTRUM
(2023)
Article
Cardiac & Cardiovascular Systems
Florentina Pluteanu, Peter Boknik, Alexander Heinick, Christiane Koenig, Frank U. Mueller, Adam Weidlich, Uwe Kirchhefer
Summary: The phosphorylation of B56 alpha at Ser(41) by PKC is involved in the regulation of myocyte Ca2+ cycling and contraction. PKC activation leads to a decrease in PP2A activity and an increase in myocyte contraction and intracellular Ca2+ signaling. PKC-mediated inhibition of PP2A also modulates the activation and inactivation kinetics of LTCC.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Teresa Bueno-Carrasco, Jorge Cuellar, Marte I. Flydal, Cesar Santiago, Trond-Andre Krakenes, Rune Kleppe, Jose R. Lopez-Blanco, Miguel Marcilla, Knut Teigen, Sara Alvira, Pablo Chacon, Aurora Martinez, Jose M. Valpuesta
Summary: Tyrosine hydroxylase (TH) is a key enzyme in the synthesis of dopamine (DA) and other catecholamines. This study used Cryo-EM to determine the structures of human TH with and without DA, as well as S40 phosphorylated TH. The study revealed the inhibitory and stabilizing effects of DA, as well as the counteraction by S40 phosphorylation, providing insights into the regulatory mechanisms of TH and dopamine homeostasis.
NATURE COMMUNICATIONS
(2022)
Article
Ecology
Emily A. Wright, Rachael C. Wiedmeier, Emma K. Roberts, David R. Pipkin, Froylan Hernandez, Joseph P. Bayouth, Warren C. Conway, Robert D. Bradley
Summary: Translocation records indicate that aoudad populations in the United States are a product of multiple human-mediated introductions. Genetic analysis shows high genetic diversity among US populations and suggests the presence of two subspecies, supporting the hypothesis of multiple introductions from multiple sources.
ECOLOGY AND EVOLUTION
(2022)
Article
Cell Biology
Heather L. Martin, Amy L. Turner, Julie Higgins, Anna A. Tang, Christian Tiede, Thomas Taylor, Sitthinon Siripanthong, Thomas L. Adams, Iain W. Manfield, Sandra M. Bell, Ewan E. Morrison, Jacquelyn Bond, Chi H. Trinh, Carolyn D. Hurst, Margaret A. Knowles, Richard W. Bayliss, Darren C. Tomlinson
Summary: This study reveals a new mechanism of kinase inhibition by capturing the intermediate activation state of PAK5. It provides a potential therapeutic target for urothelial cancer cells and suggests that inhibiting PAK5 could have anti-tumor effects on cell survival and proliferation.
Article
Microbiology
Bo Gao, Xiaoqian Gong, Shouguo Fang, Wenlian Weng, Huan Wang, Hongyan Chu, Yingjie Sun, Chunchun Meng, Lei Tan, Cuiping Song, Xusheng Qiu, Weiwei Liu, Maria Forlenza, Chan Ding, Ying Liao
Summary: Coronaviruses use the endoribonuclease nsp15 to interfere with the formation of anti-viral stress granules (SGs), reducing viral dsRNA accumulation and antagonizing PKR activation, thereby ensuring productive virus replication. Nsp15s from various coronaviruses interfere with SGs formation, possibly by targeting essential SGs assembly factors, indicating a conserved mechanism among coronaviruses to counteract host antiviral responses. This study highlights the role of nsp15 in suppressing the integral stress response and crosstalk with anti-innate immune response.
Article
Multidisciplinary Sciences
Manisha Krishnan, Madhavi D. Senagolage, Jeremy T. Baeten, Donald J. Wolfgeher, Saira Khan, Stephen J. Kron, Megan E. McNerney
Summary: CUX1 is often deleted or mutated in various tumors, but it acts as a tumor suppressor in hematopoietic cells. Previous studies suggested an oncogenic role of CUX1 in solid tumors, but our research found no evidence to support this hypothesis.
SCIENTIFIC REPORTS
(2022)
Article
Food Science & Technology
Lihong Ge, Yuli Huang, Qian Ma, Yu Wang, Rui Yang, Xinyu Yang, Yan Chen, Yuzhi Miao, Yong Zuo
Summary: Dipping grass carp fillets in certain acid solutions can effectively mitigate fish softening, inhibit cathepsin activity, and improve lysosome stability, thus protecting myosin and actin from degradation and dissociation and enhancing muscle tissue integrity.
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria I. Arifin, Lech Kaczmarczyk, Doris Zeng, Samia Hannaoui, Chi Lee, Sheng Chun Chang, Gordon Mitchell, Debbie McKenzie, Michael Beekes, Walker Jackson, Sabine Gilch
Summary: Amino acid substitutions arising from single nucleotide polymorphisms within the Prnp gene can reduce susceptibility to prion infection and prevent the development of fatal neurodegenerative diseases in mammals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Mariesa J. Slaughter, Erin K. Shanle, Abid Khan, Katrin F. Chua, Tao Hong, Lisa D. Boxer, C. David Allis, Steven Z. Josefowicz, Benjamin A. Garcia, Scott B. Rothbart, Brian D. Strahl, Ian J. Davis
Summary: The study demonstrates that HDAC inhibitors robustly increase a low-abundance histone 4 polyacetylation state, which then re-targets lysine-acetyl readers such as BRD4, affecting gene expression similarly to bromodomain inhibition.
Article
Respiratory System
David Cipolla, Jimin Zhang, Brice Korkmaz, James D. Chalmers, Jessica Basso, Daniel Lasala, Carlos Fernandez, Ariel Teper, Kevin C. Mange, Walter R. Perkins, Eugene J. Sullivan
Summary: The research found that treatment with brensocatib can reduce the activity of NE, PR3, and CatG in sputum in patients with NCFBE, and it has a broad anti-inflammatory effect.
RESPIRATORY RESEARCH
(2023)
Article
Chemistry, Medicinal
Hamid Reza Kalhor, Elham Taghikhani
Summary: The study investigated the effect of commonly used drugs on the release of warfarin bound to HSA in silico. Both s-ibuprofen and ascorbic acid were found to exhibit allosteric effects on the release of warfarin from HSA, with ibuprofen showing a stabilizing effect and ascorbic acid aiding in the release through destabilization of HSA. Molecular dynamics simulations provided valuable insights into the interactions of drugs with the protein and the mechanism of anticoagulant release.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemical Research Methods
Jens Kastenhofer, Lukas Rettenbacher, Lukas Feuchtenhofer, Juergen Mairhofer, Oliver Spadiut
Summary: The study demonstrates that induced growth repression in the E. coli X-press strain greatly alleviates the impact of metabolic burden, promoting extracellular production of recombinant protein. Temperature and specific glucose consumption rate (q(S)) are important parameters for controlling productivity and leakiness.
BIOTECHNOLOGY JOURNAL
(2021)
Editorial Material
Biochemistry & Molecular Biology
Mariusz Jaskolski, Alexander Wlodawer, Zbigniew Dauter, Wladek Minor, Bernhard Rupp
Article
Chemistry, Multidisciplinary
Bartosz Naskrecki, Mariusz Jaskolski, Zbigniew Dauter
Summary: The Euler polyhedral formula, V - E + F = 2, is a fundamental concept in mathematics with applications in geometry and topology. The Euler characteristic χ can be computed for symmetric unit polyhedra and has a topological interpretation. The Gauss-Bonnet theorem links the Euler characteristic with the general curvature of closed spaces.
JOURNAL OF APPLIED CRYSTALLOGRAPHY
(2022)
Article
Biochemistry & Molecular Biology
Marta Grzechowiak, Agnieszka Ruszkowska, Joanna Sliwiak, Anna Urbanowicz, Mariusz Jaskolski, Milosz Ruszkowski
Summary: This study investigates the structure and DNA binding characteristics of AtWRKY18, a plant transcription factor, and reveals its specific structural preferences in DNA recognition, which explains how WRKY TFs precisely regulate gene expression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Anna Cociurovscaia, Grzegorz Bujacz, Agnieszka J. Pietrzyk-Brzezinska
Summary: CusS is a component of the Escherichia coli signal transduction system, involved in responding to excessive copper ions in the cell periplasm. Understanding bacterial copper sensing mechanisms is important for reducing copper resistance and developing copper-based materials with bactericidal properties.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Microbiology
Laura Dabos, Joanna E. Raczynska, Pierre Bogaerts, Agustin Zavala, Delphine Girlich, Remy A. Bonnin, Laurent Dortet, Aurelie Peyrat, Pascal Retailleau, Bogdan I. Iorga, Mariusz Jaskolski, Youri Glupczynski, Thierry Naas
Summary: OXA-48-producing Enterobacterales have disseminated globally, with several variants reported, differing by a few amino acid substitutions or deletions, mostly in the /35-/36 loop region. OXA-517, a natural variant of OXA-48, with an Arg214Lys substitution and a deletion in the β5-β6 loop, has the ability to hydrolyze extended-spectrum cephalosporins and carbapenems. This study highlights the remarkable ability of OXA-48-like carbapenemases to evolve through mutation/deletion in the β5-β6 loop to expand their hydrolysis spectrum.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Marta Ignasiak-Kciuk, Karolina Nowicka-Bauer, Marta Grzechowiak, Tina Ravnsborg, Kamil Frackowiak, Ole N. Jensen, Mariusz Jaskolski, Bronislaw Marciniak
Summary: This study investigates the sensitized photo-oxidation reaction using carboxybenzophenone (CB) as a sensitizer and a PR-10 protein (MtN13) as a quencher. It reveals the specific binding of CB in the protein's hydrophobic cavity and the amino acid residues creating adducts with the sensitizer. The study also elucidates the mechanisms of CB quenching and the influence of neighboring groups on the oxidation process.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Physical
Andrii Pyrih, Andrzej Lapinski, Sylwia Ziebab, Roman Lesyk, Mariusz Jaskolski, Andrzej K. Gzella
Summary: New compounds, 5-dimethylaminomethylidene-4-phenylamino-1,3-thiazol-2(5H)-one and 5-methoxycarbonylmethylidene-4-phenylamino-1,3-thiazol-2(5H)-one, were synthesized and studied. Their crystal structure, chemical environment, and intermolecular interactions were analyzed using various methods, including X-ray diffraction, NMR, and FT-IR spectroscopy. The compounds exhibited amine tautomeric form in both solution and solid state, and the molecular interactions were investigated with a focus on stereoisomerism and proton tautomerism. The conformational analysis revealed the preferred coplanar arrangement of the thiazolin-2-one and phenyl systems.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Physical
Tomasz Pawlak, Piotr Paluch, Rafal Dolot, Grzegorz Bujacz, Marek J. Potrzebowski
Summary: This study investigated new salts of teriflunomide with inorganic counterions using techniques such as solid-state NMR spectroscopy, X-ray diffraction, and single crystal X-ray diffraction. The results showed a conformational change in the teriflunomide molecule in the crystalline salt structures, forming an intramolecular hydrogen bond.
SOLID STATE NUCLEAR MAGNETIC RESONANCE
(2022)
Article
Biochemical Research Methods
Pawel Drozdzal, Tomasz Manszewski, Miroslaw Gilski, Krzysztof Brzezinski, Mariusz Jaskolski
Summary: The self-complementary L-d(CGCGCG)(2) hexanucleotide, which contains the enantiomeric 2'-deoxy-L-ribose, forms a right-handed Z-DNA duplex when crystallized in complex with cadaverine and potassium cations. The ultrahigh-resolution crystal structure at 0.69 angstrom resolution confirmed the right-handed structure. Mistakenly assuming the presence of 2'-deoxy-D-ribose, the X-ray diffraction data revealed the wrong hand of the structure due to the weak anomalous signal of P and K atoms. The crystal structure also showed the interaction of the cadaverinium dication and K+ cation with the Z-DNA duplex.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maciej Janicki, Anna Sciuk, Andrzej Zielezinski, Milosz Ruszkowski, Agnieszka Ludwikow, Wojciech M. Karlowski, Mariusz Jaskolski, Joanna I. Loch
Summary: We designed and produced five new variants of the EcAIII enzyme through a nature-inspired mutagenesis approach. These modified proteins were characterized using spectroscopic and crystallographic methods, confirming their enzymatic activity. The crystal structures of the variants revealed new conformational states and allowed observation of an acyl-enzyme intermediate. Moreover, we used computational methods to study how mutations at the M200 residue affect the active site and substrate binding mode of selected bacterial orthologs.
Article
Chemistry, Multidisciplinary
Andrii Pyrih, Andrzej Lapinski, Sylwia Zieba, Adam Mizera, Roman Lesyk, Mariusz Jaskolski, Andrzej K. Gzella
Summary: Three new derivatives of 5-dimethylaminomethylidene-4-phenylamino-1,3-thiazol-2(5H)-one were synthesized and their prototropic tautomerism was studied. The compounds were found to exist solely in the amino tautomeric form in both solid and liquid phases. The electronic effects, molecular conformation, and intermolecular interactions in the crystals were analyzed.
ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS
(2023)
Article
Plant Sciences
Marta Grzechowiak, Joanna Sliwiak, Mariusz Jaskolski, Milosz Ruszkowski
Summary: Glutamate dehydrogenase (GDH) is an enzyme that plays a crucial role in the nitrogen and carbon metabolism of plants. This study focuses on AtGDH2, one of the three isoforms found in Arabidopsis thaliana. The researchers discovered that the calcium binding site in AtGDH2 is different from what was previously predicted, suggesting a structural rather than catalytic role. Comparative analysis of AtGDH1 and AtGDH2 showed similar behavior, with calcium having only a minor effect. However, gene expression profiles indicate that AtGDH2 is the most prevalent isoform.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Andrii Pyrih, Andrzej Lapinski, Sylwia Zieba, Adam Mizera, Roman Lesyk, Andrzej K. Gzella, Mariusz Jaskolski
Summary: In this study, two derivatives were synthesized to investigate the structural changes associated with proton tautomerism of the amidine system. The results showed that the studied compounds exist in the amine tautomeric form in both solid and liquid states.
ACTA CRYSTALLOGRAPHICA SECTION C-STRUCTURAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Joanna I. Loch, Paulina Worsztynowicz, Joanna Sliwiak, Marta Grzechowiak, Barbara Imiolczyk, Kinga Pokrywka, Mateusz Chwastyk, Miroslaw Gilski, Mariusz Jaskolski
Summary: The genome of Rhizobium etli encodes two L-asparaginases, ReAIV and ReAV, with no similarity to well-characterized enzymes. Despite low sequence identity, ReAIV and ReAV are hypothesized to belong to the same structural class 3. Crystal structures of ReAIV confirm its similarity to ReAV but with important differences, such as peculiar hydration patterns and three internal cavities. The structures of ReAIV may provide a basis for future enzyme-engineering experiments.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Physical
Andrii Pyrih, Andrzej Lapinski, Sylwia Zieba, Adam Mizera, Roman Lesyk, Andrzej K. Gzella, Mariusz Jaskolski
Summary: In this article, we reported the recent findings of our systematic studies on the effects of phenyl-ring substituents on proton tautomerism and stereoisomerism in 4-phenylamino-1,3-thiazol-2(5H)-one derivatives. Through synthesis, spectral analysis, and crystal studies, we found that these compounds exist solely in the amino tautomeric form and exhibit a specific arrangement.
JOURNAL OF MOLECULAR STRUCTURE
(2024)