Review
Biochemistry & Molecular Biology
Surabhi Mehra, Laxmikant Gadhe, Riya Bera, Ajay Singh Sawner, Samir K. Maji
Summary: Abnormal accumulation of aggregated alpha-synuclein is a common feature in various neurodegenerative diseases, exhibiting clinical and pathological differences similar to prion disorders. Emerging evidence suggests that alpha-Syn self-assembles into conformationally diverse polymorphs, which may contribute to the clinical heterogeneity in synucleinopathies.
Article
Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Chemistry, Medicinal
Yuguang Zhao, Fredrik Svensson, David Steadman, Sarah Frew, Amy Monaghan, Magda Bictash, Tiago Moreira, Rod Chalk, Weixian Lu, Paul Fish, E. Yvonne Jones
Summary: Notum inhibitors can restore Wnt signaling which may be therapeutic for diseases such as osteoporosis and Alzheimer's. A novel class of covalent Notum inhibitors, 4-(indolin-1-yl)-4oxobutanoate esters, and their covalent adduct formation mechanisms were identified. Insights into the inhibition of Notum catalysis could lead to the development of more potent inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Qingyue Cui, Shengzhong Frank Liu, Kui Zhao
Summary: In the past three years, metal-free perovskites have gained significant interest as promising candidates for next-generation wearable electronics. However, the relationship between the structural details and properties of these perovskites is not well understood. This review summarizes recent insights into their structural and functional aspects, explaining the role of molecular structure in the packing structure and resulting properties. It also discusses important factors and challenges in designing molecular structures for future applications, aiming to enrich the library of potential structures and applications for metal-free perovskites.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Michal Zielinski, Jaeok Park, Barry Sleno, Albert M. Berghuis
Summary: Macrolides, commonly used antibiotics, face resistance due to enzymatic cleavage by erythromycin esterases (Eres) like EreA. Limited research has been done on Eres, but a study on EreC provides insight into the catalytic mechanism of Eres as metal-independent hydrolases. Substrate assays and residue conservation analysis suggest two active site archetypes within the Ere enzyme family.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Anlian Huang, Linjing Tong, Xiaoxue Kou, Rui Gao, Zhi-Wei Li, Siming Huang, Fang Zhu, Guosheng Chen, Gangfeng Ouyang
Summary: This contribution comprehensively investigates the biomineralization of zeolite imidazole frameworks for one-step synthesis of an enzyme-MOF biocomposite. The study reveals that the biomineralization ability depends on the ZIF organic linker, and the biocatalytic function is highly related to the ZIF mineral species and their microstructures. Additionally, the protective effect of ZIF mineral on the hosted enzyme is associated with the synergistic effect of size dimension and chemical microenvironment of the ZIF pores.
Review
Biotechnology & Applied Microbiology
Jose Vicente Carratala, Anna Aris, Elena Garcia-Fruitos, Neus Ferrer-Miralles
Summary: Endolysins, bacteriophage-encoded enzymes, can be used as potential antibacterial agents. Genetic engineering techniques allow customization of their properties and activity against specific bacterial targets, enabling personalized therapies for bacterial infections. Some endolysins can cross the outer membrane of Gram-negative bacteria, enhancing their affinity towards the bacterial surface and membrane permeabilization. However, there is still a need for specific guidelines on implementing modifications to improve the bactericidal effectiveness of endolysins.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Hongwen Chen, Shahbaz Ahmed, Hongtu Zhao, Nadia Elghobashi-Meinhardt, Yaxin Dai, Jae Hun Kim, Jeffrey G. McDonald, Xiaochun Li, Chia-Hsueh Lee
Summary: Sphingosine-1-phosphate (S1P) is a crucial lipid molecule that regulates various physiological processes. Spinster homolog 2 (Spns2) is a transporter protein responsible for exporting S1P and initiating lipid signaling cascades. Understanding the transport mechanism of Spns2 and its inhibition has important implications for the development of therapeutic interventions. This study provides valuable insights into the structural basis of S1P transport by Spns2 and presents a novel inhibitor that attenuates its activity.
Article
Biochemistry & Molecular Biology
Deepthi Joseph, Smruti Ranjan Nayak, Aravind Penmatsa
Summary: This study investigates the structure and activity of GAT1 by modifying the dopamine transporter in Drosophila melanogaster. The findings suggest that the binding site undergoes substantial changes in order to accommodate GAT1 inhibitors, and an additional allosteric site is observed in the extracellular vestibule. The study also suggests a role for a specific motif in the selective control of neurotransmitter uptake.
Article
Biochemistry & Molecular Biology
Rajdeep Kaur, Simranjeet Singh Narang, Pritpal Singh, Bhupesh Goyal
Summary: A recent study found that C1 is a potential therapeutic drug for Alzheimer's disease. Molecular dynamics simulations were used to investigate the inhibitory mechanism of C1 against A beta(42) aggregation and BACE1 activity. The study also identified CHEMBL2019027 (C2) as a promising dual inhibitor of A beta(42) aggregation and BACE1 activity through virtual screening and molecular dynamics simulations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim
Summary: This study reveals unprecedented insights into the structure and function of CP2c, providing clues for its transcriptional regulation mechanism and potential therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andrea Tagliani, Jacopo Rossi, Christophe H. Marchand, Marcello De Mia, Daniele Tedesco, Libero Gurrieri, Maria Meloni, Giuseppe Falini, Paolo Trost, Stephane D. Lemaire, Simona Fermani, Mirko Zaffagnini
Summary: The study focuses on the catabolism of GSNO in the microalga Chlamydomonas reinhardtii, identifying two enzymatic systems with specific reliance on NADPH or NADH, one of which is named CrGSNOR1. The kinetic properties and three-dimensional structures of CrGSNOR1 were determined, revealing its strict specificity towards GSNO and NADH, as well as its resistance to oxidative modifications.
Article
Chemistry, Medicinal
Ryan R. Davis, Baoli Li, Sang Y. Yun, Alice Chan, Pradeep Nareddy, Steven Gunawan, Muhammad Ayaz, Harshani R. Lawrence, Gary W. Reuther, Nicholas J. Lawrence, Ernst Schonbrunn
Summary: The study presents a new methodology for large-scale production of JAK2 from mammalian cells, enabling the determination of crystal structures of JAK2 bound to drugs and derivatives for the first time. The results indicate the importance of shape complementarity for achieving highest activity of chiral and achiral inhibitors, which may facilitate the development of more effective JAK2 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ukhyun Jo, Yves Pommier
Summary: This article reviews the molecular characteristics and structural features of Schlafen proteins, highlighting their potential therapeutic applications in cancer management. The review also discusses the functional differentiation and differential expression of SLFN genes in various tissues and species, as well as their involvement in different cellular and tissue-specific processes.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Tao Wan, Magdalena Horova, Daisy Guiza Beltran, Shanren Li, Huey-Xian Wong, Li-Mei Zhang
Summary: WhiB7 is a distinct subclass of transcription factors in the WhiB-Like (Wbl) family, interacting with the primary sigma factor (sigma(A)(4)) in RNA polymerase holoenzyme to regulate gene expression through its DNA-binding motif, the AT-hook. This study reveals the structural basis of functional divergence between the two subclasses of Wbl proteins in Mycobacterium tuberculosis through high-resolution structural analysis and molecular approaches.
Article
Zoology
Eric F. Wuesthoff, Todd K. Fuller, Christopher Sutherland, Jason M. Kamilar, Rindrahatsarana Ramanankirahina, Romule Rakotondravony, Sarah Rouse, Ute Radespiel
Summary: This study investigated the spatial distributions and densities of mouse lemurs in northwestern Madagascar, revealing that habitat types have different impacts on the two species, suggesting that the generalist species utilizes a wider range of habitats more evenly compared to the specialist species.
JOURNAL OF MAMMALOGY
(2021)
Correction
Zoology
Eric F. Wuesthoff, Todd K. Fuller, Christopher Sutherland, Jason M. Kamilar, Rindrahatsarana Ramanankirahina, Romule Rakotondravony, Sarah Rouse, Ute Radespiel
JOURNAL OF MAMMALOGY
(2021)
Article
Chemistry, Multidisciplinary
Madhu Nagaraj, Zahra Najarzadeh, Jonathan Pansieri, Henrik Biverstal, Greta Musteikyte, Vytautas Smirnovas, Steve Matthews, Cecilia Emanuelsson, Janne Johansson, Joel N. Buxbaum, Ludmilla Morozova-Roche, Daniel E. Otzen
Summary: The study analyzes the impact of four different human chaperones on the aggregation process of functional amyloids in bacterial biofilms, showing that they primarily target primary nucleation during fibrillation rather than elongation or secondary nucleation, and the inhibition efficiency is correlated with their affinity for monomeric CsgA and FapC.
Article
Crystallography
Amit Kumar, Xu Zhang, Oscar Vadas, Fisentzos A. Stylianou, Nicolas Dos Santos Pacheco, Sarah L. Rouse, Marc L. Morgan, Dominique Soldati-Favre, Steve Matthews
Summary: A model for parasitic motility has been proposed, suggesting that parasite actin is connected to surface adhesins through a glideosome-associated connector protein (GAC). GAC is responsible for transmitting force to surface adhesins, rather than generating force. Proper connection between actin and adhesins is crucial for motility and invasion.
Correction
Biochemistry & Molecular Biology
Punam Rattu, Flo Glencross, Sophie L. Mader, Chris-Kriton Skylaris, Stephen J. Matthews, Sarah L. Rouse, Syma Khalid
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Ian R. Kelsall, Elisha H. McCrory, Yingqi Xu, Cheryl L. Scudamore, Sambit K. Nanda, Paula Mancebo-Gamella, Nicola T. Wood, Axel Knebel, Stephen J. Matthews, Philip Cohen
Summary: The E3 ligase activity of HOIL-1 is essential for preventing the accumulation of toxic polysaccharide deposits, as it ubiquitylates serine and threonine residues in proteins. HOIL-1 can monoubiquitylate glycogen and alpha 1:4-linked maltoheptaose, facilitating their removal from cells and preventing the formation of polyglucosan.
Article
Multidisciplinary Sciences
Peipei Zhang, Xiaohui Zhao, Yawen Wang, Ke Du, Zhihao Wang, Jianfeng Yu, Gang Chang, Steve Matthews, Hongliang Wang, Bing Liu
Summary: The HU protein is crucial for bacterial cell viability and serves as an antibiotic target. This study reveals that Gp46 from bacteriophage SPO1 can inhibit HU, leading to growth defects in bacteria. Through structural analysis, it is found that Gp46 occupies the DNA binding site of HU, thus preventing DNA binding. This discovery provides valuable insights into developing antibacterial and anti-malaria drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Kaining Zhang, Shanshan Li, Yawen Wang, Zhihao Wang, Nancy Mulvenna, Hang Yang, Peipei Zhang, Huan Chen, Yan Li, Hongliang Wang, Yongxiang Gao, Sivaramesh Wigneshweraraj, Steve Matthews, Kaiming Zhang, Bing Liu
Summary: In this study, we report a phage-encoded enolase inhibitor protein, Gp60, which can inhibit bacterial growth and peptidoglycan synthesis by disrupting the structure of enolase. This phage-inspired disassembly of enolase represents an alternative strategy for the development of antimicrobial drugs.
Article
Multidisciplinary Sciences
Georg Meisl, Catherine K. Xu, Jonathan D. Taylor, Thomas C. T. Michaels, Aviad Levin, Daniel Otzen, David Klenerman, Steve Matthews, Sara Linse, Maria Andreasen, Tuomas P. J. Knowles
Summary: The study reveals that both disease-related proteins and proteins with functional roles in biology are capable of self-replication. However, the rate of self-replication is insignificant on the biologically relevant time scale for proteins fulfilling structural roles, while disease-related proteins can self-replicate quickly within the associated disease's time scale.
Article
Biochemistry & Molecular Biology
Xeni Miliara, Takashi Tatsuta, Akinori Eiyama, Thomas Langer, Sarah L. Rouse, Steve Matthews
Summary: The PRELID-TRIAP1 family is responsible for lipid transfer in mitochondria. The lipid binding is mediated by an extended, water-mediated hydrogen bonding network. Disruption of this network by mutation R53E results in lipid release from the protein.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2023)
Article
Chemistry, Medicinal
John M. Hickey, Shaleem I. Jacob, Andrew S. Tait, Fatemeh Dastjerdi Vahid, Joseph Barritt, Sarah Rouse, Alexander Douglas, Sangeeta B. Joshi, David B. Volkin, Daniel G. Bracewell
Summary: Adenovirus vectors have become important vaccines, and electron microscopy and mass spectrometry can be used to analyze virus morphology and proteins, which helps to understand the product heterogeneity and purity, and contributes to the monitoring of viral vaccine quality during the process.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
