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Articles 1 - 12 of 12
Full-Text Articles in Biochemistry
Structural Analysis Of Neutralizing Epitopes Of The Sars-Cov-2 Spike To Guide Therapy And Vaccine Design Strategies, Maxwell T. Finkelstein , '22, Adam G. Mermelstein , '21, Emma Parker Miller , '22, Paul C. Seth , '22, Erik-Stephane D. Stancofski , '21, Daniela Fera
Structural Analysis Of Neutralizing Epitopes Of The Sars-Cov-2 Spike To Guide Therapy And Vaccine Design Strategies, Maxwell T. Finkelstein , '22, Adam G. Mermelstein , '21, Emma Parker Miller , '22, Paul C. Seth , '22, Erik-Stephane D. Stancofski , '21, Daniela Fera
Chemistry & Biochemistry Faculty Works
Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike’s receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure …
Structure-Guided Molecular Grafting Of A Complex Broadly Neutralizing Viral Epitope, G. Bajic, M. J. Maron, T. M. Caradonna, M. Tian, Adam Mermelstein , '21, Daniela Fera, G. Kelsoe, M. Kuraoka, A. G. Schmidt
Structure-Guided Molecular Grafting Of A Complex Broadly Neutralizing Viral Epitope, G. Bajic, M. J. Maron, T. M. Caradonna, M. Tian, Adam Mermelstein , '21, Daniela Fera, G. Kelsoe, M. Kuraoka, A. G. Schmidt
Chemistry & Biochemistry Faculty Works
Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a “universal” influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use noncirculating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These “resurfaced” HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization, we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and …
The Effects Of Framework Mutations At The Variable Domain Interface On Antibody Affinity Maturation In An Hiv-1 Broadly Neutralizing Antibody Lineage, Jeffrey O. Zhou , '19, Hussain A. Zaidi , '22, Therese Ton , '19, Daniela Fera
The Effects Of Framework Mutations At The Variable Domain Interface On Antibody Affinity Maturation In An Hiv-1 Broadly Neutralizing Antibody Lineage, Jeffrey O. Zhou , '19, Hussain A. Zaidi , '22, Therese Ton , '19, Daniela Fera
Chemistry & Biochemistry Faculty Works
Understanding affinity maturation of antibodies that can target many variants of HIV-1 is important for vaccine development. While the antigen-binding site of antibodies is known to mutate throughout the co-evolution of antibodies and viruses in infected individuals, the roles of the mutations in the antibody framework region are not well understood. Throughout affinity maturation, the CH103 broadly neutralizing antibody lineage, from an individual designated CH505, altered the orientation of one of its antibody variable domains. The change in orientation was a response to insertions in the variable loop 5 (V5) of the HIV envelope. In this study, we generated CH103 …
Identification Of Novel Autoinducer-2 Receptors In Clostridia Reveals Plasticity In The Binding Site Of The Lsrb Receptor Family, I. M. Torcato, M. R. Kasal, P. H. Brito, Stephen T. Miller, K. B. Xavier
Identification Of Novel Autoinducer-2 Receptors In Clostridia Reveals Plasticity In The Binding Site Of The Lsrb Receptor Family, I. M. Torcato, M. R. Kasal, P. H. Brito, Stephen T. Miller, K. B. Xavier
Chemistry & Biochemistry Faculty Works
Autoinducer-2 (AI-2) is unique among quorum-sensing signaling molecules, as it is produced and recognized by a wide variety of bacteria and thus facilitates interspecies communication. To date, two classes of AI-2 receptors have been identified: the LuxP-type, present in the Vibrionales, and the LsrB-type, found in a number of phylogenetically distinct bacterial families. Recently, AI-2 was shown to affect the colonization levels of a variety of bacteria in the microbiome of the mouse gut, including members of the genus Clostridium, but no AI-2 receptor had been identified in this genus. Here, we identify a noncanonical, functional LsrB-type receptor in Clostridium …
Structural Insights From Hiv-Antibody Co-Evolution And Related Immunization Studies, Jeffrey O. Zhou , '19, Therese Ton , '19, Julia W. Morriss , '19, Diep Nguyen , '19, Daniela Fera
Structural Insights From Hiv-Antibody Co-Evolution And Related Immunization Studies, Jeffrey O. Zhou , '19, Therese Ton , '19, Julia W. Morriss , '19, Diep Nguyen , '19, Daniela Fera
Chemistry & Biochemistry Faculty Works
Human immunodeficiency virus type 1 (HIV-1) is a rapidly evolving pathogen and causes the acquired immunodeficiency syndrome (AIDS) in humans. There are ~30-35 million people infected with HIV around the world, and ~25 million have died since the first reported cases in 1981. Additionally, each year 2-3 million people become newly infected and more than one million die of AIDS. An HIV-1 vaccine would help halt an AIDS pandemic, and efforts to develop a vaccine have focused on targeting the HIV-1 envelope, Env, found on the surface of the virus. A number of chronically infected individuals have been shown to …
Short-Chained Oligo(Ethylene Oxide)-Functionalized Gold Nanoparticles: Realization Of Significant Protein Resistance, Kathryn R. Riley, C. M. Sims, I. T. Wood, D. J. Vanderah, M. L. Walker
Short-Chained Oligo(Ethylene Oxide)-Functionalized Gold Nanoparticles: Realization Of Significant Protein Resistance, Kathryn R. Riley, C. M. Sims, I. T. Wood, D. J. Vanderah, M. L. Walker
Chemistry & Biochemistry Faculty Works
Protein corona formed on nanomaterial surfaces play an important role in the bioavailability and cellular uptake of nanomaterials. Modification of surfaces with oligoethylene glycols (OEG) are a common way to improve the resistivity of nanomaterials to protein adsorption. Short-chain ethylene oxide (EO) oligomers have been shown to improve the protein resistance of planar Au surfaces. We describe the application of these EO oligomers for improved protein resistance of 30 nm spherical gold nanoparticles (AuNPs). Functionalized AuNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. Capillary electrophoresis (CE) was used for separation and quantitation of AuNPs …
Redox-Active Nanomaterials For Nanomedicine Applications, C. M. Sims, S. K. Hanna, D. A. Heller, C. P. Horoszko, M. E. Johnson, A. R. Montoro Bustos, V. Reipa, Kathryn R. Riley, B. C. Nelson
Redox-Active Nanomaterials For Nanomedicine Applications, C. M. Sims, S. K. Hanna, D. A. Heller, C. P. Horoszko, M. E. Johnson, A. R. Montoro Bustos, V. Reipa, Kathryn R. Riley, B. C. Nelson
Chemistry & Biochemistry Faculty Works
Nanomedicine utilizes the remarkable properties of nanomaterials for the diagnosis, treatment, and prevention of disease. Many of these nanomaterials have been shown to have robust antioxidative properties, potentially functioning as strong scavengers of reactive oxygen species. Conversely, several nanomaterials have also been shown to promote the generation of reactive oxygen species, which may precipitate the onset of oxidative stress, a state that is thought to contribute to the development of a variety of adverse conditions. As such, the impacts of nanomaterials on biological entities are often associated with and influenced by their specific redox properties. In this review, we overview …
Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing, C. H. Stuart, Kathryn R. Riley, O. Boyacioglu, D. M. Herpai, W. Debinski, S. Qasem, F. C. Marini, C. L. Colyer, W. H. Gmeiner
Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing, C. H. Stuart, Kathryn R. Riley, O. Boyacioglu, D. M. Herpai, W. Debinski, S. Qasem, F. C. Marini, C. L. Colyer, W. H. Gmeiner
Chemistry & Biochemistry Faculty Works
Breast cancer (BC) results in ≃40,000 deaths each year in the United States and even among survivors treatment of the disease may have devastating consequences, including increased risk for heart disease and cognitive impairment resulting from the toxic effects of chemotherapy. Aptamer-mediated drug delivery can contribute to improved treatment outcomes through the selective delivery of chemotherapy to BC cells, provided suitable cancer-specific antigens can be identified. We report here the use of capillary electrophoresis in conjunction with next generation sequencing to develop the first vitronectin (VN) binding aptamer (VBA-01; Kd 405 nmol/l, the first aptamer to vitronectin (VN; Kd = …
Processing The Interspecies Quorum-Sensing Signal Autoinducer-2 (Ai-2) Characterization Of Phospho-(S)-4,5-Dihydroxy-2,3-Pentanedione Isomerization By Lsrg Protein, J. C. Marques, P. Lamosa, Caitlin Elizabeth Russell , '11, R. Ventura, C. D. Maycock, M. F. Semmelhack, Stephen T. Miller, K. B. Xavier
Processing The Interspecies Quorum-Sensing Signal Autoinducer-2 (Ai-2) Characterization Of Phospho-(S)-4,5-Dihydroxy-2,3-Pentanedione Isomerization By Lsrg Protein, J. C. Marques, P. Lamosa, Caitlin Elizabeth Russell , '11, R. Ventura, C. D. Maycock, M. F. Semmelhack, Stephen T. Miller, K. B. Xavier
Chemistry & Biochemistry Faculty Works
The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible …
Identification Of Functional Lsrb-Like Autoinducer-2 Receptors, C. S. Pereira, Anna Katherine De Regt , '09, P. H. Brito, Stephen T. Miller, K. B. Xavier
Identification Of Functional Lsrb-Like Autoinducer-2 Receptors, C. S. Pereira, Anna Katherine De Regt , '09, P. H. Brito, Stephen T. Miller, K. B. Xavier
Chemistry & Biochemistry Faculty Works
Although a variety of bacterial species have been reported to use the interspecies communication signal autoinducer-2 (AI-2) to regulate multiple behaviors, the molecular mechanisms of AI-2 recognition and signal transduction remain poorly understood. To date, two types of AI-2 receptors have been identified: LuxP, present in Vibrio spp., and LsrB, first identified in Salmonella enterica serovar Typhimurium. In S. Typhimurium, LsrB is the ligand binding protein of a transport system that enables the internalization of AI-2. Here, using both sequence analysis and structure prediction, we establish a set of criteria for identifying functional AI-2 receptors. We test our predictions experimentally, …
The Crystal Structure Of The Escherichia Coli Autoinducer-2 Processing Protein Lsrf, Zamia Caridad Diaz , '09, K. B. Xavier, Stephen T. Miller
The Crystal Structure Of The Escherichia Coli Autoinducer-2 Processing Protein Lsrf, Zamia Caridad Diaz , '09, K. B. Xavier, Stephen T. Miller
Chemistry & Biochemistry Faculty Works
Many bacteria produce and respond to the quorum sensing signal autoinducer-2 (AI-2). Escherichia coli and Salmonella typhimurium are among the species with the lsr operon, an operon containing AI-2 transport and processing genes that are up regulated in response to AI-2. One of the Lsr proteins, LsrF, has been implicated in processing the phosphorylated form of AI-2. Here, we present the structure of LsrF, unliganded and in complex with two phospho-AI-2 analogues, ribose-5-phosphate and ribulose-5-phosphate. The crystal structure shows that LsrF is a decamer of (alpha beta)(8)-barrels that exhibit a previously unseen N-terminal domain swap and have high structural homology …
Sinorhizobium Meliloti, A Bacterium Lacking The Autoinducer-2 (Ai-2) Synthase, Responds To Ai-2 Supplied By Other Bacteria, C. S. Pereira, J. R. Mcauley, M. E. Taga, K. B. Xavier, Stephen T. Miller
Sinorhizobium Meliloti, A Bacterium Lacking The Autoinducer-2 (Ai-2) Synthase, Responds To Ai-2 Supplied By Other Bacteria, C. S. Pereira, J. R. Mcauley, M. E. Taga, K. B. Xavier, Stephen T. Miller
Chemistry & Biochemistry Faculty Works
Many bacterial species respond to the quorum-sensing signal autoinducer-2 (AI-2) by regulating different niche-specific genes. Here, we show that Sinorhizobium meliloti, a plant symbiont lacking the gene for the AI-2 synthase, while not capable of producing AI-2 can nonetheless respond to AI-2 produced by other species. We demonstrate that S. meliloti has a periplasmic binding protein that binds AI-2. The crystal structure of this protein (here named SmlsrB) with its ligand reveals that it binds (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF), the identical AI-2 isomer recognized by LsrB of Salmonella typhimurium. The gene encoding SmlsrB is in an operon with orthologues of the lsr …