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Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.endoglycosidase | Fc glycosylation | glycoengineered antibodies | homogeneous antibodies | sugar oxazoline

Drug-resistant bacteria have caused serious medical problems in recent years, and the need for new antibacterial agents is undisputed. Transglycosylase, a multidomain membrane protein essential for cell wall synthesis, is an excellent target for the development of new antibiotics. Here, we determined the X-ray crystal structure of the bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli in complex with its inhibitor moenomycin to 2.16-Å resolution. In addition to the transglycosylase and transpeptidase domains, our structure provides a complete visualization of this important antibacterial target, and reveals a domain for protein-protein interaction and a transmembrane helix domain essential for substrate binding, enzymatic activity, and membrane orientation.antibacterial development ͉ antibiotic resistance ͉ membrane protein structure ͉ peptidoglycan synthesis ͉ protein-protein interaction I n the last decade, the prevalence and occasional outbreaks of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), have posed appalling hurdles in the treatment of bacterial infections (1, 2). New antibacterial agents are, as a result, in desperate demand to combat these pernicious antibiotic-resistant problems that can otherwise cause life-or-death struggles.Bacteria cell wall is a mesh-like structure of cross-linked peptidoglycan, which is essential to scaffold the cytoplasmic membrane and to maintain structural integrity of the cell (3). Cell wall synthesis at the membrane surface is mainly carried out by the membrane-bound enzymes, transpeptidases and transglycosylases, and inhibitors of the transpeptidase are among the most popular antibiotics in clinical use today (3).Escherichia coli PBP1b is a bifunctional transglycosylase, also known as peptidoglycan glycosyltransferase or murein synthase. It contains a transmembrane (TM) helix, 2 enzymatic domains [transglycosylase (TG) and transpeptidase (TP)] (4), and a domain composed of Ϸ100 aa residues between TM and TG with unknown structure and functionality (Fig. 1B). For Ͼ50 years, TP has been the main target for 2 most important classes of antibiotics: ␤-lactams (e.g., penicillin and methicillin) and glycopeptides (e.g., vancomycin). Not too long after they were introduced, resistant bacteria had emerged rapidly and caused serious medical problems. In contrast, resistant strains against moenomycin, the only natural inhibitor to TG from Streptomyces, have rarely been found. The development of new antibiotics against TG has been highly anticipated (5), and not until recently have the molecular structures of TG been available, even with the TM structure undefined.Two crystal structures of transglycosylase, a bifunctional transglycosylase from S. aureus (referred to as SaPBP2) and a transglycosylase domain from Aquifex aeolicus (referred to as AaPGT), have been determined recently with their TM domain or TM and TP domains removed, respectively (6-8). These structur...

Three types of CuO nanostructures—the nanorod, nanofiber, and nanoparticle—have been grown by using a self-catalytic growth process at 400, 500, and 600 °C, respectively. Field-emission (FE) properties of the CuO nanostructures were investigated. The results indicated that the FE current was significantly affected by the morphologies of the CuO samples. Typical turn-on voltage for the CuO nanofiber array was detected at about 6–7 V/μm with an emission area of 1 mm2. Based on Fowler–Nordheim plot, the values of work function for the nanofiber array were estimated in ranges of 0.56 to 2.62 and 0.30 to 1.39 eV from a two-stage linearity plot. X-ray photoelectron spectroscopy analysis showed no obvious changes in chemical composition of the nanofiber array before and after FE tests. According to the analyses, the highly ordered CuO nanofiber array can be a promising candidate for FE emitters.

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