Article
Chemistry, Multidisciplinary
Benedikt Prasser, Lisa Schoner, Lin Zhang, Oliver Einsle
Summary: The final step of denitrification involves the reduction of nitrous oxide to N-2 by Cu-dependent nitrous oxide reductase (N2OR). The assembly of N2OR is mediated by a metallochaperone encoded by the nos gene cluster, with Cu-A and Cu-Z metal centers. While only Cu-I is delivered to the enzyme, the presence of Zn-II is crucial for the functionality and structural integrity of the chaperone.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Abigail R. Orun, Ethan T. Shields, Sara Dmytriw, Ananya Vajapayajula, Caroline K. Slaughter, Christopher D. Snow
Summary: Researchers have designed isoreticular cocrystals as scaffolds for DNA-binding molecules. These cocrystals have tunable DNA-DNA junctions and can accommodate different guest molecules during crystallization. The design principles can be applied to existing cocrystals to develop programmable scaffolds for DNA-binding molecules.
Article
Chemistry, Multidisciplinary
Yohei Katsuyama, Kaoru Sone, Ayaka Harada, Seiji Kawai, Naoki Urano, Naruhiko Adachi, Toshio Moriya, Masato Kawasaki, Kazuo Shin-ya, Toshiya Senda, Yasuo Ohnishi
Summary: The study determined the structure of FmoA3 using X-ray crystallography and cryogenic electron microscopy, revealing the accommodation of alpha-methyl-l-serine in the active site. The Cy domains of FmoA2 and FmoA3 catalyze different reactions, with the Cy domain of FmoA3 potentially losing its donor PCP binding activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Ying Yu, Junsong Guo, Zhengjun Cai, Yingchen Ju, Jun Xu, Qiong Gu, Huihao Zhou
Summary: This study utilized fragment screening and X-ray crystallography to identify new building blocks and binding mechanisms for the discovery of new GyrB inhibitors. Some chemical fragments were found to affect enzyme activity, providing new insights for the design of GyrB inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Jiaxing Wang, Duane D. Miller, Wei Li
Summary: This review summarizes the crystal structures of tubulin in complexes with various CBSIs, aiming to facilitate the discovery of new generations of tubulin inhibitors.
DRUG DISCOVERY TODAY
(2022)
Article
Multidisciplinary Sciences
Eugenia M. Clerico, Alexandra K. Pozhidaeva, Rachel M. Jansen, Can Ozden, Joseph M. Tilitsky, Lila M. Gierasch
Summary: This research investigated how Hsp70 binds to full-length client proteins by analyzing complex structures and experiments, revealing that many sequences can choose from multiple binding modes and binding preference depends on the compatibility of substrate residue side chains with binding pockets. The study also found that multiple chaperones can simultaneously bind to multiple sites on the protein substrate, and these sites behave independently.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Charles Eldrid, Mire Zloh, Constantina Fotinou, Tamas Yelland, Lefan Yu, Filipa Mota, David L. Selwood, Snezana Djordjevic
Summary: Vascular endothelial growth factors (VEGFs) are essential regulators for blood and lymphatic vessels, interacting with neuropilins and tyrosine kinase receptors. The selectivity of neuropilins and VEGF receptors in binding to VEGF proteins affects their physiological roles. Studies have shown that conformational preferences of VEGF-derived peptides beyond the C-terminal arginine contribute to the ligand selectivity of neuropilins. These findings have implications for designing selective antagonists of neuropilin functions.
Article
Multidisciplinary Sciences
Akimitsu Higuchi, Wataru Shihoya, Masae Konno, Tatsuya Ikuta, Hideki Kandori, Keiichi Inoue, Osamu Nureki
Summary: SzRs, a newly identified rhodopsin family in Asgard archaea, exhibit unique kinetic behaviors in inward H+ release compared to other H+ pumps. The crystal structure of SzR AM_5_00977 revealed that key residues and structural features are different from other microbial rhodopsins, suggesting a distinct mechanism for inward H+ release.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Cen Chen, Ziyuan Fang, Zhen Huang
Summary: Crystallization phasing and obtaining high-quality crystals are major challenges for X-ray crystallographic analysis of nucleic acids. In this study, the authors addressed these challenges by incorporating selenium atoms into DNA duplexes, which resulted in larger and higher quality crystals compared to standard DNA crystals. These findings provide a simple strategy to overcome crystallization challenges in nucleic acid crystallography.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Immunology
Estelle K. Ronayne, Shaun C. Peters, Joseph S. Gish, Celena Wilson, H. Trent Spencer, Christopher B. Doering, Pete Lollar, P. Clint Spiegel, Kenneth C. Childers
Summary: This study reports the X-ray crystal structure of a B domain-deleted bioengineered fVIII bound to the non-classical antibody inhibitor, G99. While binding to G99 does not disrupt the overall domain architecture of fVIII, the C2 domain undergoes an approximately 8 angstrom translocation along with breaking multiple domain-domain interactions. Analysis of normalized B-factor values reveals a decrease in thermal motion in certain solvent-exposed loops in the presence of inhibitory antibodies, providing insights into the structural dynamics of binding non-classical inhibitors and the cooperative nature between anti-C1 and anti-C2 domain inhibitors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Hai Li, Chia-Ying Huang, Elena G. Govorunova, Oleg A. Sineshchekov, Adrian Yi, Kenneth J. Rothschild, Meitian Wang, Lei Zheng, John L. Spudich
Summary: The crystal structure of bromide-bound GtACR1 reveals structural changes that relax the constrictions of the channel and involve a novel salt-bridge switch mechanism. These findings suggest that substrate binding induces a transition from an inactivated state to a pre-activated state in the dark, facilitating channel opening.
Article
Biochemistry & Molecular Biology
Mustafa Bal, Aysegul Kose, Seyit Ali Gungor
Summary: This study synthesized benzimidazole compounds containing benzophenone group according to the literature and investigated their DNA binding properties using UV-vis and photoluminescence spectroscopy. The structures of the compounds were determined using methods such as FT-IR, H-1, C-13 NMR, UV-vis, photoluminescence spectroscopy, and X-ray crystallography. Information about the binding types, binding mode, and binding energies of the compounds with DNA were collected using UV-vis, photoluminescence spectroscopy, and viscosity tests. Binding interactions were also investigated using molecular docking. The calculated binding constants (Kb) for substances A, B, and C were found to be 3.0 x 10(4), 7.0 x 10(4), and 3.0 x 10(4) M-1, respectively. Compound B showed the best DNA binding activity in in vitro studies. It is believed that these synthesized compounds may have potential in cancer drug research as DNA binding agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Gabriel Javitt, Alisa Kinzel, Nava Reznik, Deborah Fass
Summary: Zymogen granule membrane protein 16 (ZG16) is a protein produced in organs that secrete enzymes and other proteins into the digestive tract, with the ability to bind microbial pathogens. The CXXC motif on ZG16 contributes to its activity, and can be oxidized by specific enzymes to engage in redox reactions.
Article
Spectroscopy
Pranjalee Yadav, Rohit Kumar, S. Srikrishna, Anoop Kumar Pandey, Lokman H. Choudhury, Chandan Upadhyay, Vinod P. Singh
Summary: This work presents the synthesis, characterization, crystal structure and spectroscopic investigations of isophthalohydrazide based probe. The probe selectively detects Al3+ and Cu2+ in aqueous ethanol via fluorometric and colorimetric methods. Sensing mechanism is explored with UV-Vis, fluorescence spectroscopy and H-1 NMR titration, and confirmed with computational results.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Chemistry, Multidisciplinary
Jiali Yang, Takahiro Mori, Xingxing Wei, Yudai Matsuda, Ikuro Abe
Summary: The novel isomerase NsrQ from Aspergillus novofumigatus plays a key role in the biosynthesis of fungal tetrahydroxanthones by catalyzing a two-step isomerization reaction. Through biochemical and structural characterizations, it was found that NsrQ and its homologue Dcr3 utilize Glu and His residues as acid-base catalysts and important hydrophobic residues for shaping the active site pocket for substrate binding. The crystal structures of NsrQ and Dcr3 revealed their cone-shaped alpha + beta barrel fold and similarities to the nuclear transport factor 2-like superfamily enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Analytical
Sebastian Schmutzler, Michele Woelk, Ralf Hoffmann
Summary: D-glucose and D-fructose can react with amino groups, leading to proteins glycated at lysine residues. Metabolic diseases like diabetes elevate sugar levels, favoring glycation reactions and the formation of advanced glycation end products (AGEs) linked to diabetic complications and cardiovascular diseases. Current analytical methods for differentiating and quantifying Amadori- and Heyns-modified proteins in complex samples are limited.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alexandra Brakel, Andor Krizsan, Renke Itzenga, Carl N. Kraus, Laszlo Otvos, Ralf Hoffmann
Summary: Proline-rich antimicrobial peptide ARV-1502 and its analogs exhibit strong antimicrobial effects against Enterobacteriaceae bacteria. The study reveals that these analogs exert antimicrobial activity by binding to the bacterial 70S ribosome, and the binding site overlaps with other antimicrobial peptides and antibiotics. Substitutions in the ribosomal binding motif affect binding and inhibitory activity, and substitutions with higher hydrophobicity or positive net charge improve ribosome binding, translation inhibition, and bacterial uptake.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Reimund Goss, Daniela Volke, Lina Emilia Werner, Ronja Kunz, Marcel Kansy, Ralf Hoffmann, Christian Wilhelm
Summary: In this study, fucoxanthin chlorophyll protein (FCP) complexes of the centric diatom Thalassiosira pseudonana were prepared using low concentrations of a mild detergent and sucrose gradient ultracentrifugation. Two main FCP fractions were observed in the sucrose gradients, each with different protein, lipid, and pigment composition. Mass spectrometry analysis revealed the presence of the xanthophyll cycle enzyme DDE in both FCP fractions, with higher enrichment in the fraction enriched in FCP-A. In-vitro de-epoxidation assays showed a more pronounced conversion of DD to Dt in the fraction enriched in FCP-A compared to FCP-B.
Article
Medicine, Research & Experimental
Roland Bottger, Po-Han Chao, Nojoud AL Fayez, Griffin Pauli, Anne Nguyen, Lukas Hohenwarter, Nida Bilal, Gubran Khalil Mohammed, Daniel Knappe, Ralf Hoffmann, Shyh-Dar Li
Summary: Excipients in nanomedicines play a critical role in determining product quality, stability, consistency, and safety. This study developed a HPLC method combined with an ELS detector and a UV-vis detector to simultaneously analyze drugs and excipients in nanomedicines. This method can be applied to various nanodrug delivery systems and provides important information for nanomedicine formulation development.
MOLECULAR PHARMACEUTICS
(2022)
Article
Virology
Ji Luo, Alexandra Brakel, Andor Krizsan, Tobias Ludwig, Marina Motzing, Daniela Volke, Nicole Lakowa, Thomas Gruenewald, Claudia Lehmann, Johannes Wolf, Stephan Borte, Sanja Milkovska-Stamenova, Joerg Gabert, Felix Fingas, Markus Scholz, Ralf Hoffmann
Summary: This study developed an ELISA method based on the N-protein to sensitively and specifically detect SARS-CoV-2 specific IgG antibodies in human serum. The method is effective for detecting symptomatic infections and may be useful in identifying previous SARS-CoV-2 infections in vaccinated individuals.
Article
Infectious Diseases
Tobias Ludwig, Andor Krizsan, Gubran Khalil Mohammed, Ralf Hoffmann
Summary: Given the global spread of drug-resistant bacteria and the emergence of pan-resistant bacteria, there is an urgent need for antimicrobials with new mechanisms of action. Antimicrobial peptides (AMPs), including proline-rich AMPs (PrAMPs), are a promising class. In this study, a designer peptide called Api805 was created by combining the N- and C-terminal sequences of PrAMPs Api137 and drosocin. Api805 exhibited similar activity against two Escherichia coli B strains, but was inactive against E. coli K12 strain BW25113. The differences in activity could not be explained by the measured dissociation constants for 70S ribosome preparations from the different strains.
Article
Biochemical Research Methods
Pei Su, Ziyan Warneke, Daniela Volke, Michael F. Espenship, Hang Hu, Sebastian Kawa, Kaplan Kirakci, Ralf Hoffmann, Julia Laskin, Christian Wiebeler, Jonas Warneke
Summary: This study investigates the collision-induced dissociation (CID) of [Mo6X14]2- (X = Cl, Br, I) and the reactivity of fragment ions with background gases. Ion mobility measurements and theoretical calculations provide structural information. Sequential losses of MoX2 units dominate the dissociation pathways for [Mo6Cl14]2-, while loss of X radicals is the main channel for X = Br and I. Variation in mass spectra obtained using CID is observed among mass spectrometers. Ion-trap fragmentation combined with theoretical investigations indicates spontaneous losses of X radicals upon binding of O2 to [Mo6Im]- fragments (m <= 12).
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Engineering, Biomedical
Gubran Khalil Mohammed, Roland Bottger, Andor Krizsan, Daniela Volke, Marina Moetzing, Shyh-Dar Li, Daniel Knappe, Ralf Hoffmann
Summary: The prodrug strategy of linking polyethylene glycol (PEGs) with proline-rich AMP Onc72 is tested for the first time in vivo. The PEGylation protects Onc72 from degradation and provides a prolonged release, leading to stable Onc72 concentrations and high antibacterial activities. The prodrugs show promising safety margins and extended elimination half-life in mice.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Julia Kratky, Daniel Eggerichs, Thomas Heine, Sarah Hofmann, Philipp Sowa, Renato H. Weisse, Dirk Tischler, Norbert Straeter
Summary: This study presents the crystal structure of VpIndA1, an indole monooxygenase from bacterium Variovorax paradoxus EPS, and reveals the structural basis of substrate binding and stereoselectivity through substrate complex structures and force-field calculations. By redesigning the substrate cavity based on the structural information, variants with new substrate selectivity and greatly enhanced stereoselectivity were successfully generated. This research opens up new possibilities for structure-based design of these powerful biocatalysts.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Luisana Avilan, Bruce R. Lichtenstein, Gerhard Koenig, Michael Zahn, Mark D. Allen, Liliana Oliveira, Matilda Clark, Victoria Bemmer, Rosie Graham, Harry P. Austin, Graham Dominick, Christopher W. Johnson, Gregg T. Beckham, John E. McGeehan, Andrew R. Pickford
Summary: Enzyme-based depolymerization is a viable approach for recycling PET, but the concentration-dependent inhibition of IsPETase hinders its effectiveness. This study finds that the inhibition depends on incubation time, solution conditions, and PET surface area. Furthermore, this inhibition is also observed in other mesophilic PET-degrading enzymes, but not in the highly thermostable HotPETase. This work highlights the limitations of using natural mesophilic hydrolases for PET hydrolysis and the potential benefits of enhancing their thermostability.
Article
Biotechnology & Applied Microbiology
Kevin J. McNaught, Eugene Kuatsjah, Michael Zahn, Erica T. Prates, Huiling Shao, Gayle J. Bentley, Andrew R. Pickford, Josephine N. Gruber, Kelley V. Hestmark, Daniel A. Jacobson, Brenton C. Poirier, Chen Ling, Myrsini San Marchi, William E. Michener, Carrie D. Nicora, Jacob N. Sanders, Caralyn J. Szostkiewicz, Dusan Velickovic, Mowei Zhou, Nathalie Munoz, Young-Mo Kim, Jon K. Magnuson, Kristin E. Burnum-Johnson, K. N. Houk, John E. McGeehan, Christopher W. Johnson, Gregg T. Beckham
Summary: Deciphering the mechanisms of bacterial fatty acid biosynthesis is crucial for both engineering bacterial hosts and developing antibiotics. This study reveals that Pseudomonas putida KT2440 has three distinct pathways for initiating fatty acid biosynthesis, with the third pathway being a novel alternative. The findings provide new opportunities for various biotechnological and biomedical applications.
METABOLIC ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Kyle Mangano, Dorota Klepacki, Irueosa Ohanmu, Chetana Baliga, Weiping Huang, Alexandra Brakel, Andor Krizsan, Yury S. Polikanov, Ralf Hoffmann, Nora Vazquez-Laslop, Alexander S. Mankin
Summary: The antimicrobial peptide Drosocin (Dro) from fruit flies inhibits protein synthesis by arresting ribosomes at stop codons, similar to apidaecin (Api) from honeybees. However, the interactions of Dro and Api with the ribosome target are distinct, with Dro relying on multiple amino acid residues throughout the PrAMP. Single-residue substitutions can enhance Dro's on-target activity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Tobias Claff, Jonathan G. Schlegel, Jan H. Voss, Victoria J. Vaassen, Renato H. Weisse, Robert K. Y. Cheng, Sandra Markovic-Mueller, Denis Bucher, Norbert Straeter, Christa E. Mueller
Summary: The authors report the crystal structures of A(2A)AR in complex with Etrumadenant, revealing a previously unknown interaction. These findings have implications for the design of selective receptor antagonists.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marina Moetzing, Matthias Blueher, Thomas Grunwald, Ralf Hoffmann
Summary: This study aimed to develop a sensitive and clinically applicable ELISA method for the quantification of the glycation site HSAK414 in plasma samples. An indirect ELISA method was established using the generated antibody mAb 50D8, demonstrating good antibody performance and precision. The reliability and correlation of the method were validated by comparing with results from liquid chromatography-mass spectrometry. The study suggests that the glycation site HSAK414 could be a potential biomarker for diabetes mellitus, and ELISA is a suitable method for high-throughput screening and routine laboratory analysis.
Article
Chemistry, Medicinal
Shenghua Gao, Letian Song, Katharina Sylvester, Beatrice Mercorelli, Arianna Loregian, Karoly Toth, Renato H. Weisse, Abibe Useini, Norbert Straeter, Mianling Yang, Bing Ye, Ann E. Tollefson, Christa E. Mueller, Xinyong Liu, Peng Zhan
Summary: This study discovered a novel nonpeptidic M-pro inhibitor, GC-78-HCl, with promising antiviral activity and favorable pharmacokinetic profile. The compound exhibited potent antiviral activities against various SARS-CoV-2 variants, as well as HCoV-OC43 and HCoV-229E, indicating its potential broad-spectrum anticoronaviral activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
