A5002200873- Enzyme Structure and Function
- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Protein Interaction Studies and Fluorescence Analysis
- Blood disorders and treatments
- Allergic Rhinitis and Sensitization
- Food Allergy and Anaphylaxis Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Structure and Dynamics
- Protein purification and stability
- Chemical Synthesis and Analysis
- Contact Dermatitis and Allergies
- Amino Acid Enzymes and Metabolism
- GABA and Rice Research
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- Monoclonal and Polyclonal Antibodies Research
- Legume Nitrogen Fixing Symbiosis
- Computational Drug Discovery Methods
- Antibiotic Resistance in Bacteria
- Peanut Plant Research Studies
- Bacterial Genetics and Biotechnology
- Microbial Metabolism and Applications
- Oral and gingival health research
University of Virginia
2013-2025
Cancer Research UK Scotland Institute
2022
Charlottesville Medical Research
2018
Joint Center for Structural Genomics
2013-2016
New York Structural Biology Center
2012-2016
Adam Mickiewicz University in Poznań
2008-2015
International Institute of Molecular and Cell Biology
2014
Argonne National Laboratory
2013
University of Asmara
2011
Abstract Ribonuclease H-like (RNHL) superfamily, also called the retroviral integrase groups together numerous enzymes involved in nucleic acid metabolism and implicated many biological processes, including replication, homologous recombination, DNA repair, transposition RNA interference. The RNHL superfamily proteins show extensive divergence of sequences structures. We conducted database searches to identify members (including those previously unknown), yielding >60 000 unique...
Abstract The availability of purified and active protein is the starting point for majority in vitro biomedical, biochemical, drug discovery experiments. use polyhistidine affinity tags has resulted great increases efficiency purification process, but can negatively affect structure and/or activity measurements. Similarly, buffer molecules may perturb conformational stability a or its activity. During determination Gcn5‐related N ‐acetyltransferase (GNAT) from Pseudomonas aeruginosa...
Allergic reactions to peanuts and tree nuts are major causes of anaphylaxis in the United States. We compare different properties natural recombinant versions Ara h 1, a peanut allergen, through structural, immunologic, bioinformatics analyses. Small angle x-ray scattering studies show that 1 forms higher molecular weight aggregates solution. In contrast, full-length protein is partially unfolded exists as monomer. The crystal structure core (residues 170-586) shows central part allergen has...
Abstract Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub synthesis remains elusive due to transient nature handover. Here, we present structure a chemically trapped complex E2 UBE2K covalently linked donor and acceptor di-Ub, primed by RING E3. The reveals basis recognition active site residues C-terminal Ub-associated (UBA) domain, impart specificity catalysis. Furthermore,...
Abstract The misidentification of a protein sample, or contamination sample with the wrong protein, may be potential reason for non‐reproducibility experiments. This problem occur in process heterologous overexpression and purification recombinant proteins, as well proteins from natural sources. If contaminated misidentified is used crystallization, many cases not detected until structures are determined. In case functional studies, years. Here several procedures that can successfully...
The first albumin structure in complex with testosterone and the hormone's binding affinity measured two methods.
Due to a combination of efforts from individual laboratories and structural genomics centers, there has been surge in the number members Gcn5-related acetyltransferasesuperfamily that have structurally determined within past decade. Although three-dimensional structures is increasing steadily, we know little about functions these enzymes. Part difficulty assigning for this superfamily lack information regarding how substrates bind active site protein. The majority do not show ligand bound...
Ragweed allergens affect several million people in the United States and Canada. To date, only two ragweed allergens, Amb t 5 a 11, have their structures determined deposited to Protein Data Bank. Here, we present of methylated allergen 8, 8 presence poly(l-proline), Art v 4 (mugwort allergen). are panallergens belonging profilin family proteins. They share significant sequence structural similarities, which results cross-recognition by IgE antibodies. Molecular immunological properties...
Polyamines within the cell are tightly regulated by spermidine/spermine N-acetyltransferase (SSAT) enzymes. While several SSATs have been investigated in different bacterial species, there is still a significant gap knowledge about which proteins functional many organisms. For example, while it known that Pseudomonas aeruginosa synthesizes polyamine spermidine, SSAT acetylates this molecule and its importance regulating intracellular polyamines remains unknown. We previously identified...
The Gcn5-related N-acetyltransferase (GNAT) superfamily is a large group of evolutionarily related acetyltransferases, with multiple paralogs in organisms from all kingdoms life. functionally characterized GNATs have been shown to catalyze the transfer an acetyl acetyl-coenzyme A (Ac-CoA) amine wide range substrates, including small molecules and proteins. are prevalent implicated myriad aspects eukaryotic prokaryotic physiology, but functions many remain unknown. In this work, we used...
Der p 1 is a major allergen from the house dust mite, Dermatophagoides pteronyssinus, that belongs to papain-like cysteine protease family. To investigate antigenic determinants of 1, we determined two crystal structures in complex with Fab fragments mAbs 5H8 or 10B9. Epitopes for these 1-specific Abs are located different, nonoverlapping parts molecule. Nevertheless, surface area and identity amino acid residues involved hydrogen bonds between Ab similar. The epitope mAb 10B9 only showed...
Enzymes in the Gcn5-related
Deeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge types molecules that can be acylated by this important superfamily enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions proteins is ideal, their alternative promiscuous vitro capabilities provide insight into key active site interactions. Additionally, exploited selectively modify complex...
Dexamethasone, a widely used corticosteroid, has recently been reported as the first drug to increase survival chances of patients with severe COVID-19. Therapeutic agents, including dexamethasone, are mostly transported through body by binding serum albumin. Here, structure albumin in complex dexamethasone is reported. Dexamethasone binds site 7, which also for commonly nonsteroidal anti-inflammatory drugs and testosterone, suggesting potentially problematic competition. This study bridges...