Article
Multidisciplinary Sciences
Alicja Razew, Cedric Laguri, Alicia Vallet, Catherine Bougault, Magdalena Kaus-Drobek, Izabela Sabala, Jean-Pierre Simorre
Summary: NMR and mass spectrometry were used to investigate the interaction between short peptidoglycan fragments and two evolutionarily related peptidases of the M23 family, lysostaphin and LytM. The study reveals that peptidoglycan cross-linking affects the activity and specificity of these enzymes differently.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Spencer Mitchell, Deeptak Verma, Karl E. Griswold, Chris Bailey-Kellogg
Summary: This study systematically investigates the role of bacterial autolysins in biological processes and developed a pipeline to analyze the autolysin repertoires of various pathogenic bacteria, revealing commonalities and differences among them. Furthermore, unannotated sequence regions within the lytic enzymes were identified, which may contain new domains with important functions.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nima Ghahremani Nezhad, Raja Noor Zaliha Raja Abd Rahman, Yahaya M. Normi, Siti Nurbaya Oslan, Fairolniza Mohd Shariff, Thean Chor Leow
Summary: Engineered thermostable microbial enzymes are widely used in various industrial sectors, but improving thermostability often sacrifices enzyme activity. It is crucial to select common and compatible strategies to improve both thermostability and activity, in order to reduce mutant libraries and screening time. This review analyzes three protein engineering approaches (directed evolution, rational design, and semi-rational design) and discusses integrative strategies that improve activity and thermostability by manipulating protein structure. The goal is to overcome the trade-off between thermostability and activity for industrial enzymes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Yang Wang, Michael R. Kanost, Haobo Jiang
Summary: Serine protease cascades have evolved as a rapid defense response in both vertebrates and invertebrates. This study investigates the autoactivation mechanism of a protease called proHP14 in response to bacterial recognition. The results reveal the importance of interactions between proHP14 and peptidoglycan recognition proteins, which play a crucial role in the activation of the immune response. This research contributes to our understanding of the molecular mechanisms of immune defense.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Fisheries
Bing Ma, Xinghong Wang, Qianxia Liu, Yue Zhao, Zhiping Su, Yujia Chen, Youming Hou, Zhanghong Shi
Summary: This study aimed to determine the role of a peptidoglycan recognition protein (PGRP), RfPGRP-S3, in the immunity of the red palm weevil (RPW). The results showed that RfPGRP-S3 can recognize Gram-positive bacteria and affect the expression of antimicrobial peptide genes. Silencing RfPGRP-S3 significantly compromised the ability of individuals to clear pathogenic bacteria, and dramatically decreased the survival rate of RPW larvae challenged with Staphylococcus aureus. These findings demonstrate the important role of RfPGRP-S3 in the immune response of RPW.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Saidbakhrom Saidjalolov, Zainab Edoo, Matthieu Fonvielle, Louis Mayer, Laura Iannazzo, Michel Arthur, Melanie Etheve-Quelquejeu, Emmanuelle Braud
Summary: Carbapenems have been optimized to target Gram-negative bacteria producing extended-spectrum beta-lactamases for the treatment of tuberculosis. The introduction of substituents at position C2 has shown to increase drug efficacy. Synthesizing peptido-carbapenems with a phenethylthio substituent at C2 demonstrated improved activity compared to the reference drug meropenem.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Cell Biology
Nanfang Peng, Helen H. H. Kang, Yan Feng, Alexander M. M. Minikes, Xuejun Jiang
Summary: Macroautophagy/autophagy is an important cellular survival mechanism in cancer, and its inhibition has potential therapeutic applications. This study found that inhibiting autophagy not only enhanced chemotherapy efficacy in glioblastoma (GBM) but also induced therapy-induced senescence of GBM cells. Additionally, autophagy inhibition altered the profile of senescence-associated secretory phenotype (SASP), leading to enhanced paracrine senescence, polarization of anti-tumor macrophages, and reduced recruitment of pro-tumor neutrophils. This study reveals the functional link between autophagy and senescence and suggests using autophagy blockage for senescence-mediated antitumor immunity.
Article
Biochemistry & Molecular Biology
Jessica L. Bohrhunter, Patricia D. A. Rohs, Grasiela Torres, Rachel Yunck, Thomas G. Bernhardt
Summary: The peptidoglycan (PG) cell wall surrounding bacterial cells is crucial for cell integrity and is a key antibiotic target. MltG has been identified as a potential terminase for PG synthesis in Escherichia coli, acting by cleaving PG glycans during active synthesis.
MOLECULAR MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
David Scheerer, Bharat V. Adkar, Sanchari Bhattacharyya, Dorit Levy, Marija Iljina, Inbal Riven, Orly Dym, Gilad Haran, Eugene I. Shakhnovich
Summary: Enzymes have a crucial role in controlling chemical reactions and achieving high catalytic efficiency and selectivity. The three-domain enzyme adenylate kinase (AK) catalyzes phosphotransfer between ATP and AMP. Our study using single-molecule FRET spectroscopy reveals that AMP inhibits AK by promoting faster and more cooperative domain closure by ATP, leading to an increased population of the closed state. We developed a model based on experimentally observed opening and closing rates, explaining the complex activity of AK, particularly substrate inhibition, and highlighting the importance of protein motions in enzymatic activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
Xue Liu, Mingjin Wang, Xiandao Pan, Xiaoguang Chen, Jing Jin, Xiaojian Wang
Summary: In this study, a series of ABZI STING agonist derivatives with potent STING-activating effects were developed through a structure-activity relationship study of amidobenzimidazole monomer. Compound 72, as a representative compound, significantly activated the STING-TBK1-IRF3 signaling pathway and increased the mRNA and protein levels of IFN-beta, CXCL10, and IL-6. It was also highly selective for human STING and did not activate m-STING.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Irene Louise van Grinsven, Eliza C. Martin, Andrei-Jose Petrescu, Richard Kormelink
Summary: Plant disease immunity relies on the recognition of pathogens and immune pathway activation. Nod-like receptors, such as Tsw, play a crucial role in this process. Tsw, a Nod-like resistance gene with unusually large LRR domains, confers resistance against TSWV. However, the function of the majority of the LRR structure remains unclear.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yubao Shan, Xiaoling He, Zi Wang, Xiali Yue, Jiang Zhu, Yunhuang Yang, Maili Liu
Summary: This study investigated the structure of Clostridium perfringens autolysin (CpAcp) SH3b domains through NMR spectroscopy and structural simulation, revealing that the ten SH3b domains have different ligand-binding abilities, with SH3b1/2 showing unique specificity and additional binding sites compared to other SH3b domains.
Article
Microbiology
Genevieve S. Dobihal, Josue Flores-Kim, Ian J. Roney, Xindan Wang, David Z. Rudner
Summary: The WaIR-WalK signaling system is crucial for the homeostatic control of cell wall hydrolases in Bacillus subtilis.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Cristina Gallego-Paramo, Noelia Hernandez-Ortiz, Pedro Garcia, Margarita Menendez
Summary: In this study, we investigated the tuning of natural lysin activity by acquiring enzymatic active domains (EADs) and cell wall binding domains (CWBDs). By combining EAD of Skl and cell wall choline-binding domain (CBD) of LytA, a chimeric lysin QSLA with superior antibacterial capacity was produced. The QSLA showed increased bacterial killing and extended substrate range compared to parental enzymes. This study provides a novel approach to design superior lysins and presents a promising therapeutic perspective.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Microbiology
Miaomiao Shi, Stephanie E. Willing, Hwan Keun Kim, Olaf Schneewind, Dominique Missiakas
Summary: Staphylococcus aureus causes reiterative and chronic infections by utilizing its protein A (SpA) to bind to immunoglobulins, interfering with B cell responses and altering the specific immune responses of the host.
