Bacterial ATP-binding cassette (ABC) importers play critical roles in nutrient acquisition and are potential antibacterial targets. However, structural bases for their inhibition are poorly defined. These pathways typically rely on substrate binding proteins (SBPs), which are essential for substrate recognition, delivery, and transporter function. We report the crystal structure of a Staphylococcus aureus SBP for Mn(II), termed MntC, in complex with FabC1, a potent antibody inhibitor of the MntABC pathway. This pathway is essential and highly expressed during S. aureus infection and facilitates the import of Mn(II), a critical cofactor for enzymes that detoxify reactive oxygen species (ROS). Structure-based functional studies indicate that FabC1 sterically blocks a structurally conserved surface of MntC, preventing its interaction with the MntB membrane importer and increasing wild-type S. aureus sensitivity to oxidative stress by more than 10-fold. The results define an SBP blocking mechanism as the basis for ABC importer inhibition by an engineered antibody fragment.
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http://dx.doi.org/10.1016/j.str.2015.01.020 | DOI Listing |
Am J Reprod Immunol
January 2025
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Objectives: Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer.
Methods: TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes.
Results: Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival.
BMJ Open
January 2025
Oriola Finland Oy, Espoo, Uusimaa, Finland
Background: The use of new biological medicines as standard treatment is expected to increase substantially and cover new therapeutic indications in the near future. Interchange of biological medicines in pharmacies increases the need for patient guidance.
Objectives: The study aims to gain a patient perspective on biological medicine users' needs and wishes regarding patient guidance by exploring what kind of information patients wish to receive and to further investigate the potential differences in needs between originator biological medicine users and biosimilar users.
MAbs
December 2025
SeromYx Systems, Woburn, MA, USA.
The field of antibody therapeutics is rapidly growing, with over 210 antibodies currently approved or in regulatory review and ~ 1,250 antibodies in clinical development. Antibodies are highly versatile molecules that, with strategic design of their antigen-binding domain (Fab) and the domain responsible for mediating effector functions (Fc), can be used in a wide range of therapeutic indications. Building on many years of progress, the biopharmaceutical industry is now advancing innovative research and development by exploring new targets and new formats and using antibody engineering to fine-tune functions tailored to specific disease requirements.
View Article and Find Full Text PDFAnalyst
January 2025
College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, China.
The M13 phage carries approximately 5 copies of the pIII protein, each of which is capable of displaying a single-chain variable fragment (scFv) that targets a specific antigen. This feature enables the M13 phage to be widely employed in the construction of scFv libraries, thereby facilitating the identification of antibodies with high specificity and affinity for target antigens. In this study, mice were immunized three times with (strain C50041) to induce diverse antibodies.
View Article and Find Full Text PDFJ Hazard Mater
January 2025
Chinese-German Joint Laboratory for Natural Product Research, Shaanxi International Cooperation Demonstration Base, Shaanxi University of Technology, Hanzhong, Shaanxi 723000, China; Centre of Molecular & Environmental Biology, Department of Biology, University of Minho, Braga 4710-057, Portugal; Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada. Electronic address:
The increasing environmental prevalence of micro/nano plastics (MNPs) has raised significant concerns regarding their potential impact on human health, particularly in terms of immunotoxicity. However, the direct effects of MNPs on immune molecules, especially how they may influence protein liquid-liquid phase separation (LLPS)-a critical process implicated in various aspects of immune function-remain largely unexplored. This study addresses this gap by investigating the effects of polystyrene nanoparticles (PS NPs) with different surface modifications and sizes on LLPS in immunoglobulin Y (IgY) antibodies, critical components of the avian immune system.
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