Article
Virology
Kai Ren, Honggang Sun, Limin Chen, Ningning Chen, Lu Yu
Summary: MxA inhibits ZIKV replication by activating the type I interferon signaling pathway, without affecting virus entry. Upregulation of MxA is accompanied by increased expression levels of RIG-I, MDA5, TLR3, IRF3, IFN alpha, and IFNI3. The inhibitory effect of MxA on ZIKV replication is abolished in cells lacking the type I interferon receptor (IFNAR).
Article
Biotechnology & Applied Microbiology
Martina Anzaghe, Stefanie Kronhart, Marc A. Niles, Lena Hoecker, Monica Dominguez, Georg Kochs, Zoe Waibler
Summary: Studies have shown that some negative-strand RNA viruses can induce type I interferon responses in an IFNAR-independent manner, rather than relying on the IFNAR feedback loop.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Yen-Lin Huang, Ching-Yeu Liang, Vera Labitzky, Danilo Ritz, Tiago Oliveira, Cecile Cumin, Manuela Estermann, Tobias Lange, Arun V. Everest-Dass, Francis Jacob
Summary: ITGA2 is a highly glycosylated transmembrane protein in ovarian cancer tissue and cell lines, with N- and O-glycosylation sites playing a crucial role in collagen and laminin binding. Mutants lacking N-glycosylated ITGA2 show decreased adherence to collagen, potentially due to increased proteasome degradation through poly-ubiquitination.
Article
Biochemistry & Molecular Biology
Edwin T. Gibbs II, Chad A. Lerner, Mark A. Watson, Hoi-Shan Wong, Akos A. Gerencser, Martin D. Brand
Summary: Superoxide/hydrogen peroxide production by site IQ in complex I occurs during both reverse and forward electron transport, and is equally sensitive to S1QELs, rotenone, and piericidin A. A new assay is introduced to determine the direction of electron flow through complex I. The results show that superoxide/hydrogen peroxide production by site IQ in cells is S1QEL-sensitive and occurs during forward electron transport.
BIOCHEMICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Hua-Yang Guo, Hong-Xi He, Bao-Suo Liu, Nan Zhang, Ke-Cheng Zhu, Dian-Chang Zhang
Summary: Interferon regulatory factor 7 (IRF7) regulates type I interferon (IFN) genes in the immune response against bacteria. In this study, IRF7 and two IFNa3s (IFNa3 and IFNa3-like) were identified in A. latus. AlIRF7 is expressed in various organs with high levels in the spleen and liver. S. iniae challenge promoted the expression of AlIRF7 in multiple organs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(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
Biochemistry & Molecular Biology
Joan Teyra, Megan McLaughlin, Alex Singer, Abdellali Kelil, Andreas Ernst, Frank Sicheri, Sachdev S. Sidhu
Summary: PDZ domains play crucial roles in signaling pathways by recognizing specific C-terminal amino acid sequences in proteins. In vitro evolution strategies can be used to explore the specific recognition capabilities of PDZ domains and provide insights into their molecular basis. Evolved PDZ variants greatly expand our understanding of their specificities and may have applications in synthetic biology.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Physical
Wenbo Yu, David J. Weber, Alexander D. MacKerell
Summary: Covalent drug design plays a significant role in drug discovery by forming a covalent bond with targeted residues, leading to a more effective therapeutic approach. Computational methods can identify reactive residues, test potential reactivities, and predict noncovalent contributions to binding. SILCS, a functional group mapping approach, considers protein flexibility, functional group, and protein desolvation along with functional group-protein interactions. SILCS-Covalent, an integrated workflow, can qualitatively and quantitatively inform covalent drug discovery.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemistry & Molecular Biology
Sonali Chaturvedi, Michael Pablo, Marie Wolf, Daniel Rosas-Rivera, Giuliana Calia, Arjun J. Kumar, Noam Vardi, Kelvin Du, Joshua Glazier, Ruian Ke, Matilda F. Chan, Alan S. Perelson, Leor S. Weinberger
Summary: This study found that disrupting transcriptional negative feedback can effectively inhibit viral replication and confer a high genetic barrier to resistance, providing a new approach for developing novel antimicrobials.
Article
Neurosciences
Kiki J. Chen, Ryan Yoshimura, Clarissa Adriana Edmundo, Tri Minh Truong, Olivier Civelli, Amal Alachkar, Geoffrey W. Abbott
Summary: By investigating the GABA binding site that activates KCNQ3, it was found that this direct interaction has significant effects on mouse behavior, especially in regulating nociception and stress responses. This finding provides new targets for treating neurological and psychiatric disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Brandon M. Bordeau, Lubna Abuqayyas, Toan D. Nguyen, Ping Chen, Joseph P. Balthasar
Summary: Our group has developed a strategy to increase antibody penetration in solid tumors by transiently inhibiting antibody-antigen binding. The strategy was validated experimentally and showed increased efficacy of antibody-based therapeutics in HER2+ xenograft bearing mice. We also developed a mechanistic pharmacokinetic model to predict within-tumor exposure of the antibody and a pharmacodynamic component to predict the therapeutic effect. The study has important implications for optimizing antibody-cytotoxin penetration and efficacy in solid tumors.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Bingyi Chen, Siting Luo, Songxuan Zhang, Yingchen Ju, Qiong Gu, Jun Xu, Xiang-Lei Yang, Huihao Zhou
Summary: Reveromycin A (RM-A) selectively inhibits eukaryotic cytoplasmic isoleucyltRNA synthetase (IleRS). The co-crystal structure suggests that RM-A molecule occupies the tRNA(Ile) binding site of Saccharomyces cerevisiae IleRS, and that RM-A cooperates with isoleucine or isoleucyl-adenylate for IleRS binding.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Andreas Isaak, Clemens Dobelmann, Friederike Theresa Fusser, Katharina Sophie Erlitz, Oliver Koch, Anna Junker
Summary: This study provides a comprehensive understanding of the orthosteric ATP-binding site of P2X receptors by characterizing various ATP derivatives and conducting in silico studies. It identifies a novel pan-P2X receptor agonist and several subtype-selective agonists. Additionally, a compound that acts as an antagonist at P2X1-4 and P2X2/3 receptors and an agonist at P2X7 receptors is developed, enabling specific investigation of P2X7 receptor function while antagonizing other P2X receptor subtypes.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Himanshu Goel, Anthony Hazel, Wenbo Yu, Sunhwan Jo, Alexander D. MacKerell
Summary: SILCS utilizes molecular simulation to obtain functional group affinity patterns for drug discovery, allowing for identification of novel ligand binding pockets, prediction of protein-ligand binding affinities, and other applications in computer-aided drug design. It represents a comprehensive approach to improve drug development processes through accuracy and throughput enhancements.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ammar Ammar, Rachel Cavill, Chris Evelo, Egon Willighagen
Summary: Protein mutations, especially in the binding site, can impact drug response. Experimental screening is time-consuming and expensive, so computational approaches are valuable in guiding these experiments.
JOURNAL OF CHEMINFORMATICS
(2023)
Article
Immunology
Ahmed Lasfar, Jeffry R. Cook, Karine A. Cohen Solal, Kenneth Reuhl, Sergei V. Kotenko, Jerome A. Langer, Debra L. Laskin
Article
Immunology
Brian J. Scaglione, Erica Salerno, Kinisha Gala, Manjing Pan, Jerome A. Langer, Howard S. Mostowski, Steven Bauer, Gerald Marti, Yu Li, Vincent K. Tsiagbe, Elizabeth S. Raveche
JOURNAL OF AUTOIMMUNITY
(2009)
Article
Multidisciplinary Sciences
Netanya G. Sandler, Steven E. Bosinger, Jacob D. Estes, Richard T. R. Zhu, Gregory K. Tharp, Eli Boritz, Doron Levin, Sathi Wijeyesinghe, Krystelle Nganou Makamdop, Gregory Q. del Prete, Brenna J. Hill, J. Katherina Timmer, Emma Reiss, Ganit Yarden, Samuel Darko, Eduardo Contijoch, John Paul Todd, Guido Silvestri, Martha Nason, Robert B. Norgren, Brandon F. Keele, Srinivas Rao, Jerome A. Langer, Jeffrey D. Lifson, Gideon Schreiber, Daniel C. Douek
Review
Immunology
SV Kotenko, JA Langer
INTERNATIONAL IMMUNOPHARMACOLOGY
(2004)
Review
Biochemistry & Molecular Biology
JA Langer, EC Cutrone, S Kotenko
CYTOKINE & GROWTH FACTOR REVIEWS
(2004)
Article
Immunology
SV Kotenko, G Gallagher, VV Baurin, A Lewis-Antes, ML Shen, NK Shah, JA Langer, F Sheikh, H Dickensheets, RP Donnelly