Article
Biochemistry & Molecular Biology
Kelly K. Barnsley, Mary Jo Ondrechen
Summary: Understanding the biochemically active amino acids in proteins is crucial for improving our understanding of enzyme function, predicting the function of unknown protein structures, and guiding enzyme engineering. This article explores recent computational chemistry-based methods for predicting active amino acids in protein 3D structures, including distal residues, and discusses their implications for functional genomics, enzyme design, and enhancing our understanding of enzyme function.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Victor P. Kutyshenko, Dmitry A. Prokhorov, Galina Mikoulinskaia, Nikolai Molochkov, Alexander Y. Yegorov, Svetlana Paskevich, Vladimir N. Uversky
Summary: The study revealed that the binding of Zn2+ ion to the active site of EndoRB49 peptidase causes conformational rearrangements similar to those observed in the EndoT5 peptidase, leading to the formation of a catalytically active form of the enzyme. Therefore, the binding of Zn2+ ion to the active site of EndoRB49 peptidase is a necessary and sufficient condition for the functioning of this protein.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Markus Zweckstetter
Summary: The AlphaFold2 method has shown the ability to accurately predict protein structures in solution, matching well with experimental data, and holds promise as a powerful tool for studying structural changes in proteins.
Article
Chemistry, Physical
Huan Yan, Selim Alayoglu, Weiqiang Wu, Yongbo Zhang, Eric Weitz, Peter C. Stair, Justin M. Notestein
Summary: The study discovered that depositing differently sized boronic acids into the micropores of silica supports results in different distributions of surface borate species after calcination. These materials exhibit a wide range of rates in ODHP but similar selectivity, indicating they differ only in the numbers of active sites. The correlation between identified features and catalyst activity confirms hydroxylated nonring boron as the likely active site, providing a target for future catalyst syntheses.
Article
Plant Sciences
Meixia Ruan, Hao Li, Ying Zhang, Ruoqi Zhao, Jun Zhang, Yingjie Wang, Jiali Gao, Zhuan Wang, Yumei Wang, Dapeng Sun, Wei Ding, Yuxiang Weng
Summary: The major light-harvesting complex of photosystem II (LHCII) plays a dual regulatory role in the process of non-photochemical quenching to prevent reactive oxygen formation. LHCII undergoes reversible conformational transitions to switch between a light-harvesting state and an energy-quenching state. Cryo-electron microscopy structures and quantum calculations reveal that LHCII acts as a controlling switch for the transition between light capture and excess energy dissipation in response to lateral pressure and acid-induced conformational changes.
Article
Chemistry, Physical
Wenhua Han, Pengye Liu, Mengke Zheng, Xiao Cheng Zeng, Wen Wu Xu
Summary: This study examines the effect of interfacial interactions on thiolate-protected gold nanoclusters, presenting a ring model to offer insight into these interactions and predicting a new Au-42(SR)(26) isomer with lower energy than previously crystallized isomers. The ring model provides a mechanistic understanding of interactions between protection ligands and gold cores, offering practical guidance for predicting and confirming new gold nanoclusters in future experimental synthesis.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Qiao Han, Pan Gao, Kuizhi Chen, Lixin Liang, Zhenchao Zhao, Xinlong Yao, Dong Xiao, Xiuwen Han, Guangjin Hou
Summary: Efficiency improvement in the oxide-zeolite bifunctional syngas-to-hydrocarbon catalysis requires a deep understanding of the reaction mechanism, especially for the poor initial syn-gas conversion over the oxide component. Through advanced solid-state NMR technologies, specific surface dual active sites for syngas activation were identified, and the dynamic evolution of reaction intermediates and active sites during the reaction process were elucidated at the atomic level. The in-depth understanding of the catalytic mechanism will aid in the rational design of high-performance catalysts for syngas conversion.
Article
Chemistry, Multidisciplinary
Jeffery L. White, Kuizhi Chen, Anya Zornes, Vy Nguyen, Bin Wang, Zhehong Gan, Steven P. Crossley
Summary: This study reveals the presence of at least two types of paired active sites in zeolite catalysts through NMR experiments, and finds that these paired sites play a crucial role in reactivity. Additionally, it is observed that synthetic and postsynthetic modifications affect the quantity and arrangement of these paired sites.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Eric M. Smith, Se Ferrell, Valerie L. Tokars, Alfonso Mondragon
Summary: CRISPR systems provide prokaryotes with an adaptive immune system against invading genetic material. This study presents the cryo-EM structures of the type III-A Staphylococcus epidermidis CRISPR effector complex, revealing its binding characteristics to target RNA and the production of cyclic oligoadenylates.
Article
Biology
Fangyu Liu, James Lee, Jue Chen
Summary: The ATP-binding cassette (ABC) transporter family is diverse and contains thousands of members. ABCA4 is a eukaryotic importer that transports retinal and removes toxic retinoids, mutations in which lead to impaired vision. Despite years of study, the molecular mechanism of ABCA4 remains unknown.
Article
Chemistry, Inorganic & Nuclear
Alexander L. Estrada, Leyong Wang, Gisela Hess, Frank Hampel, John A. Gladysz
Summary: This study successfully embedded metals in cage-like trans-spanning di(triaryl)phosphine ligands and synthesized corresponding compounds. The reaction mechanism and molecular structure were analyzed through crystallography and NMR spectroscopy.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Marin Yokomine, Jumpei Morimoto, Yasuhiro Fukuda, Yota Shiratori, Daisuke Kuroda, Takumi Ueda, Koh Takeuchi, Kouhei Tsumoto, Shinsuke Sando
Summary: In this study, oligo(N-methylalanine) (oligo-NMA) is proposed as a peptide-based molecular scaffold with a minimal structure and a high density of functionalizable sites. Oligo-NMA forms a defined shape in water without hydrogen-bonding networks or ring constraints. It can be easily functionalized on the nitrogens and a-carbons. The usefulness of oligo-NMA is demonstrated by the design of protein ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Konstantin Khivantsev, Nicholas R. Jaegers, Ja-Hun Kwak, Janos Szanyi, Libor Kovarik
Summary: The study identified specific sites on the surface of gamma-alumina responsible for its catalytic activity and elucidated their nature and role in the reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Jinghua Jiang, Kamal Ranabhat, Xinyu Wang, Hailey Rich, Rui Zhang, Chenhui Peng
Summary: This study demonstrates that programmable transformations of topological structures in active matter can be triggered by light irradiation, opening opportunities for designing smart active materials.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Giuseppina La Sala, Christopher Pfleger, Helena Kack, Lisa Wissler, Philip Nevin, Kerstin Bohm, Jon Paul Janet, Marianne Schimpl, Christopher J. Stubbs, Marco De Vivo, Christian Tyrchan, Anders Hogner, Holger Gohlke, Andrey I. Frolov
Summary: This study developed a structure-based three-parameter model that integrates local binding site information, coevolution information, and information on dynamic allostery to identify potentially hidden allosteric sites in ensembles of protein structures. The model successfully ranked all known allosteric pockets in the top three positions when tested on five allosteric proteins. Additionally, two novel druggable sites were identified and confirmed in MAT2A and BCKDK protein structures. This model can be used in drug discovery to identify allosteric pockets.
Article
Multidisciplinary Sciences
Salima Bahri, Robert Silvers, Brian Michael, Kristaps Jaudzems, Daniela Lalli, Gilles Casano, Olivier Ouari, Anne Lesage, Guido Pintacuda, Sara Linse, Robert G. Griffin
Summary: Magic-angle spinning (MAS) NMR spectroscopy has been widely used to study the high-resolution structures of amyloid-beta (A beta) and other fibrils, but it suffers from low sensitivity. In this study, the drawbacks of MAS NMR were overcome by using two relatively recent techniques: H-1 detection and dynamic nuclear polarization (DNP). The results showed improved sensitivity and allowed for nearly complete resonance assignment and structural analysis of A beta fibrils.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Guillaume A. Petit, Biswaranjan Mohanty, Roisin M. McMahon, Stefan Nebl, David H. Hilko, Karyn L. Wilde, Martin J. Scanlon, Jennifer L. Martin, Maria A. Halili
Summary: This study identified two fragments that bind to the DsbA protein from Burkholderia pseudomallei, providing a potential starting point for the development of more potent antimicrobial compounds.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tina Arndt, Gabriele Greco, Benjamin Schmuck, Jessica Bunz, Olga Shilkova, Juanita Francis, Nicola M. Pugno, Kristaps Jaudzems, Andreas Barth, Jan Johansson, Anna Rising
Summary: The development of miniature spider silk proteins has made large-scale fiber production economically feasible by producing stronger artificial silks. This research shows that the method can be used for economically feasible bulk-scale production.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Tanguy Le Marchand, Tobias Schubeis, Marta Bonaccorsi, Piotr Paluch, Daniela Lalli, Andrew J. Pell, Loren B. Andreas, Kristaps Jaudzems, Jan Stanek, Guido Pintacuda
Summary: The development of H-1 detection and fast MAS technology has led to significant breakthroughs in solid-state NMR, improving signal intensity and resolution. The switch from traditional detection methods to H-1 enables faster analysis of high molecular weight biological components and provides successful strategies for studying protein structure and conformational dynamics.
Editorial Material
Biochemistry & Molecular Biology
Medoune Sarr, Kristine Kitoka, Kellie-Ann Walsh-White, Margit Kaldmaee, Rimants Metlans, Kaspar Tars, Alessandro Mantese, Dipen Shan, Michael Landreh, Anna Rising, Jan Johansson, Kristaps Jaudzems, Nina Kronqvist
Summary: The N-terminal domain of spider silk proteins plays a crucial role in the storage and assembly of spider silk. In this study, the solution and crystal structures of the N-terminal domain of the flagelliform spidroin were determined. It was found that the electrostatic intermolecular interaction between specific residues is conserved, but the protonation events involve different residues compared to another type of spidroin. This suggests that the overall mechanism of pH-dependent dimerization is conserved but can be mediated by different pathways in different silk types.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Zigmantas Toleikis, Raitis Bobrovs, Agne Janoniene, Alons Lends, Mantas Ziaunys, Ieva Baronaite, Vytautas Petrauskas, Kristine Kitoka, Vytautas Smirnovas, Kristaps Jaudzems
Summary: S100A9 interacts with α-synuclein and influences the aggregation process. This study analyzed the interaction using F-19 and 2D N-15-H-1-HSQC NMR spectroscopy and studied the aggregation properties of these two proteins. The results showed that α-synuclein interacts with S100A9 at specific regions, which are also essential in the first step of aggregation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Raitis Bobrovs, Emils Edgars Basens, Laura Drunka, Iveta Kanepe, Sofija Matisone, Karlis Kristofers Velins, Victor Andrianov, Gundars Leitis, Diana Zelencova-Gopejenko, Dace Rasina, Aigars Jirgensons, Kristaps Jaudzems
Summary: In this study, the selectivity-determining factors in drugs targeting pathogen aspartic proteases were explored. It was found that selectivity could be achieved by targeting the flap loop with hydrophobic substituents.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Olga Bobileva, Raitis Bobrovs, Evelina Elva Sirma, Iveta Kanepe, Anna L. Bula, Liene Patetko, Anna Ramata-Stunda, Solveiga Grinberga, Aigars Jirgensons, Kristaps Jaudzems
Summary: SARS-CoV-2 nsp14 guanine-N7-methyltransferase is crucial for viral RNA translation, and compound 5p was developed as a potent inhibitor targeting both SAM and mRNA-binding pockets of nsp14. It exhibited subnanomolar inhibitory activity and enhanced cell membrane permeability compared to the parent inhibitor, suggesting its potential as a bisubstrate inhibitor for further development in combating the virus.
Article
Biochemistry & Molecular Biology
Diana Zelencova-Gopejenko, Melita Videja, Aiga Grandane, Linda Pudnika-Okincica, Anda Sipola, Karlis Vilks, Maija Dambrova, Kristaps Jaudzems, Edgars Liepinsh
Summary: Heart-type fatty-acid binding protein (FABP3) is a cytosolic lipid transport protein that binds fatty acids (FAs) and protects cells from the detrimental effects of long-chain acylcarnitines (LCACs). Through cytotoxicity assays, nuclear magnetic resonance, and isothermal titration calorimetry, the study characterizes the novel binding mechanism between FABP3 and LCACs. The findings demonstrate that FABP3 competes with FAs for binding sites and has a concentration-dependent protective mechanism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Felix Torres, Matthias Buetikofer, Gabriela R. R. Stadler, Alois Renn, Harindranath Kadavath, Raitis Bobrovs, Kristaps Jaudzems, Roland Riek
Summary: Although nuclear magnetic resonance (NMR) is commonly used in fragment-based drug design, its lack of sensitivity has limited its implementation in high-throughput screening. However, photochemically induced dynamic nuclear polarization (photo-CIDNP) is a promising method that can improve the sensitivity of NMR. This research demonstrates the detection of weak binders using low micromolar concentrations, exploiting the polarization enhancement provided by photo-CIDNP and achieving faster interaction detection compared to standard techniques. Furthermore, an automated flow-through platform and a photo-CIDNP fragment library are presented, providing a comprehensive approach for fragment-based screening.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
James Schiemer, Andrew Maxwell, Reto Horst, Shenping Liu, Daniel P. Uccello, Kris Borzilleri, Nisha Rajamohan, Matthew F. Brown, Matthew F. Calabrese
Summary: Targeted protein degradation using heterobifunctional chimeras can expand the druggable proteome and target proteins that are difficult to inhibit with small molecules. This study explores the role of covalent modification in targeted protein degradation using Bruton's tyrosine kinase, demonstrating its compatibility with the degradation mechanism.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Arenida Bartkeviciene, Aldona Jasukaitiene, Inga Zievyte, Darius Stukas, Sandra Ivanauskiene, Daiva Urboniene, Toivo Maimets, Kristaps Jaudzems, Astra Vitkauskiene, Jason Matthews, Zilvinas Dambrauskas, Antanas Gulbinas
Summary: This study found that the expression level of aryl-hydrocarbon receptor (AHR) plays a crucial role in immune dysregulation in pancreatic cancer, suggesting that it could be a potential target for early diagnostics and personalized therapeutics.
Article
Medical Laboratory Technology
Pavol Mikolka, Nina Kronqvist, Marie Haegerstrand-Bjorkman, Kristaps Jaudzems, Petra Kosutova, Maros Kolomaznik, Mihkel Saluri, Michael Landreh, Andrea Calkovska, Tore Curstedt, Jan Johansson
Summary: This study developed a novel surfactant called Combo that showed promising therapeutic effects in both premature and adult rabbit models of respiratory distress syndrome (RDS), which is caused by insufficient lung surfactant. Combo proved to be more resistant to inhibition and demonstrated better improvement in respiratory parameters compared to the natural-derived surfactant currently used in clinical practice for treating RDS. This makes Combo an attractive candidate for developing new therapies against human ARDS.
TRANSLATIONAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Rebecca L. L. Whitehouse, Wesam S. S. Alwan, Olga V. V. Ilyichova, Ashley J. J. Taylor, Indu R. R. Chandrashekaran, Biswaranjan Mohanty, Bradley C. C. Doak, Martin J. J. Scanlon
Summary: Fragment-based drug design relies on structural information obtained through X-ray crystallography to evolve fragments into lead-like compounds through structure-based design. The composition of compound libraries can be optimized to probe binding hot spots on protein surfaces.
RSC MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Tanguy Le Marchand, Tobias Schubeis, Marta Bonaccorsi, Piotr Paluch, Daniela Lalli, Andrew J. Pell, Loren B. Andreas, Kristaps Jaudzems, Jan Stanek, Guido Pintacuda
Summary: H-1-detected MAS NMR has become an efficient method for investigating biomolecular structure, dynamics, and interactions by solid-state NMR, with significant advancements in sensitivity and resolution.