A5089531874- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Glycosylation and Glycoproteins Research
- Respiratory viral infections research
- Escherichia coli research studies
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Analysis
- Bacillus and Francisella bacterial research
- Protein purification and stability
- ATP Synthase and ATPases Research
- Bacterial Genetics and Biotechnology
- Bone health and treatments
- Metabolomics and Mass Spectrometry Studies
- 14-3-3 protein interactions
- Biochemical and Molecular Research
- bioluminescence and chemiluminescence research
- Viral Infectious Diseases and Gene Expression in Insects
- Genetics and Neurodevelopmental Disorders
- HER2/EGFR in Cancer Research
- CRISPR and Genetic Engineering
AstraZeneca (United States)
2023-2024
University of Kansas
2014-2022
GlaxoSmithKline (United States)
2020
University of Missouri–Kansas City
2016
Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within field of biologics. In silico tools that can streamline process antibody discovery and optimization are critical to support pipeline is growing more numerous complex every year. High-quality structural information remains for process, but antibody-antigen structures often unavailable in docking methods still unreliable. this study, DeepAb, deep learning model predicting Fv structure directly...
Abstract Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement phosphatase and transferase domains creating solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode to select enrich lariat-like ligands an...
Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for management norovirus infection. 3C-like protease is essential replication, consequently, inhibition this enzyme a fruitful avenue investigation that may lead to emergence antinorovirus therapeutics. We describe herein optimization dipeptidyl inhibitors using iterative SAR, X-ray crystallographic, and cell-based studies....
Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There currently no vaccines or small molecule therapeutics available for treatment prophylaxis norovirus infections. Norovirus 3CL protease plays vital role in viral replication by generating structural nonstructural proteins via cleavage polyprotein. Thus, molecules that inhibit may have potential therapeutic value. We describe herein structure-based design, synthesis,...
Respiratory syncytial virus (RSV) is a global public health burden for which no licensed vaccine exists. To aid development via increased understanding of the protective antibody response to RSV prefusion glycoprotein F (PreF), we performed structural and functional studies using human neutralizing (nAb) RSB1. The crystal structure PreF complexed with RSB1 reveals conformational, pre-fusion specific site V epitope unique cross-protomer binding mechanism. We identify shared features between...
Abstract Over the last two decades, therapeutic antibodies have emerged as a rapidly expanding domain within field biologics. In silico tools that can streamline process of antibody discovery and optimization are critical to support pipeline is growing more numerous complex every year. this study, DeepAb, deep learning model for predicting Fv structure directly from sequence, was used design 200 potentially stabilized variants an anti-hen egg lysozyme (HEL) antibody. We sought determine...
The 26S proteasome is a 2.5 MDa protease dedicated to the degradation of ubiquitinated proteins in eukaryotes. assembly this complex containing 66 polypeptides assisted by at least nine proteasome-specific chaperones. One these, Nas2, binds proteasomal AAA-ATPase subunit Rpt5. PDZ domain Nas2 C-terminal tail Rpt5; however, it does not require C-terminus Rpt5 for binding. Here, 1.15 Å resolution structure reported. This will provide basis further insights regarding and function assembly.
Human noroviruses are the primary cause of outbreaks acute gastroenteritis worldwide. The problem is further compounded by current lack norovirus-specific antivirals or vaccines. Noroviruses have a single-stranded, positive sense 7 to 8 kb RNA genome which encodes polyprotein precursor that processed virus-encoded 3C-like cysteine protease (NV 3CLpro) generate at least six mature nonstructural proteins. Processing essential for virus replication, consequently, NV 3CLpro has emerged as an...
Nucleoid-associated proteins (NAPs) in prokaryotes play an important architectural role DNA bending, supercoiling and compaction. In addition to roles, some NAPs also regulatory roles replication repair, act as global transcriptional regulators many bacteria. Bacteria encode multiple of them are even essential for survival. Streptococcus mutans , a dental pathogen, encodes one such NAP called histone-like protein (HLP). Here, the three-dimensional structure S. HLP has been determined 1.9 Å...
Ncb5or (NADH-cytochrome b5 oxidoreductase), a cytosolic ferric reductase implicated in diabetes and neurological diseases, comprises three distinct domains, cytochrome (b5) (b5R) domains separated by CHORD-Sgt1 (CS) domain, novel 50-residue N-terminal region. Understanding how interdomain interactions facilitate the shuttling of electrons from NAD(P)H to heme, process compares with microsomal (Cyb5A) b5R (Cyb5R3) system, is interest. A high-resolution structure domain (PDB entry 3lf5) has...
Abstract Anthrax is a severe bacterial infection caused by Bacillus anthracis , which produces tripartite toxin that includes protective antigen (PA), lethal factor (LF) and edema (EF). A series of dominant-negative mutations have been previously identified prevent the heptameric PA prepore from forming pH-induced, membrane spanning beta-barrel pore required for translocation EF LF to cytoplasm infected cell. Here we show dominant negative D425A mutation stalls formation at reversible...