A5028679389- Protein Structure and Dynamics
- Enzyme Structure and Function
- Bacterial Infections and Vaccines
- RNA and protein synthesis mechanisms
- Protein purification and stability
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Force Microscopy Techniques and Applications
- Electron Spin Resonance Studies
- Bacterial Genetics and Biotechnology
- Molecular Junctions and Nanostructures
- Hormonal and reproductive studies
- Analytical Chemistry and Chromatography
- Computational Drug Discovery Methods
- Coccidia and coccidiosis research
- Glycosylation and Glycoproteins Research
- Magnetism in coordination complexes
- Advanced MRI Techniques and Applications
- Cholesterol and Lipid Metabolism
- Bioinformatics and Genomic Networks
- Lipid Membrane Structure and Behavior
- Advanced NMR Techniques and Applications
- Fungal and yeast genetics research
- Crystallography and molecular interactions
Institute for Bioscience and Biotechnology Research
2018-2023
University of Maryland, College Park
2023
National Institute of Standards and Technology
2023
Advanced Bioscience Laboratories (United States)
2018-2023
Research Institute for Bioscience and Biotechnology
2023
University of Mary
2021-2022
University of Virginia
2014-2016
Naturally occurring metamorphic proteins have the ability to interconvert from one folded state another through either a limited set of mutations or by way change in local environment. Here, we show designed system that it is possible switch reversibly between two most common monomeric folds employing only temperature changes. We demonstrate latent 3α can be unmasked an α/β-plait topology with single V90T amino acid substitution, populating both forms simultaneously. The equilibrium these...
Abstract To better understand how amino acid sequence encodes protein structure, we engineered mutational pathways that connect three common folds (3α, β−grasp, and α/β−plait). The structures of proteins at high sequence-identity intersections in the (nodes) were determined using NMR spectroscopy analyzed for stability function. generate nodes, encoding a smaller fold is embedded structure an ~50% larger new compatible with two sets native interactions designed. This generates pairs 3α or...
Carcino-embryonic antigen-like cellular adhesion molecules (CEACAMs), members of the immunoglobulin superfamily, are responsible for cell-cell interactions and signaling events. Extracellular with CEACAMs have potential to induce phagocytosis, as is case pathogenic Neisseria bacteria. Pathogenic species express opacity-associated (Opa) proteins, which interact a subset on human cells, initiate engulfment bacterium. We demonstrate that recombinant Opa proteins reconstituted into liposomes...
The clinical efficacy and safety of protein-based drugs such as monoclonal antibodies (mAbs) rely on the integrity protein higher order structure (HOS) during product development, manufacturing, storage, patient administration. As mAb-based are becoming more prevalent in treatment many illnesses, need to establish metrics for quality attributes mAb therapeutics through high-resolution techniques is also evident. To this end, here we used a forced degradation method, time-dependent oxidation...
Labeling of proteins with deuterium is an essential tool in overcoming size limitations the application nuclear magnetic resonance (NMR) spectroscopy to larger than 30 kilodaltons (kDa). A non-originator antigen-binding fragment (Fab) NIST RM 8671 NISTmAb, so called yNIST-Fab, a ~ 50 kDa protein, 5 native disulfide linkages, that can be expressed properly folded form methylotrophic Komagataella phaffii (formerly Pichia pastoris ). Further, K. host support production perdeuterated yNIST-Fab...
Abstract We have engineered switches between the three most common small folds, 3α, 4β+α, and α/β−plait, referred to here as A, B, S, respectively. Mutations were introduced into natural S protein until sequences created that a stable S-fold in their longer (∼90 amino acid) form an alternative fold (either A or B) shorter (56 form. Five sequence pairs designed key structures determined using NMR spectroscopy. Each pair is 100% identical 56 acid region of overlap. Several rules for...
Abstract Protein sequences encoding three common small folds (3α, β–grasp, and α/β–plait) were connected in a network with high-identity intersections, termed nodes. The structures of proteins around nodes determined using NMR spectroscopy analyzed for stability binding function. To generate nodes, the amino acid sequence shorter fold (3a or β–grasp) is embedded structure ~ 50% longer α/β–plait new designed that satisfies two sets native interactions. This leads to protein pairs 3a β–grasp...