- Bacterial Genetics and Biotechnology
- Biochemical and Structural Characterization
- Light effects on plants
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Bacteriophages and microbial interactions
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Algal biology and biofuel production
- Photoreceptor and optogenetics research
- Carbohydrate Chemistry and Synthesis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- Bacterial Infections and Vaccines
- Bacterial biofilms and quorum sensing
- Protein Structure and Dynamics
- Signaling Pathways in Disease
- Antimicrobial Peptides and Activities
- Lipid Membrane Structure and Behavior
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Phylogenetic Studies
- Enzyme Production and Characterization
- Amino Acid Enzymes and Metabolism
University of Wisconsin–Madison
2014-2023
Madison Group (United States)
2010-2014
UW Health University Hospital
2011
Biologie Labor
2008
Scripps Research Institute
1995-2000
Fox Chase Cancer Center
1996
Philadelphia University
1996
Princeton University
1992
The ability of phytochromes (Phy) to act as photointerconvertible light switches in plants and microorganisms depends on key interactions between the bilin chromophore apoprotein that promote attachment photointerconversion spectrally distinct red light-absorbing Pr conformer far Pfr conformer. Using structurally guided site-directed mutagenesis combined with several spectroscopic methods, we examined roles conserved amino acids within bilin-binding domain Deinococcus radiodurans...
Preorganization is shown to endow a protein with extraordinary conformational stability. This preorganization achieved by installing side-chain substituents that impose stereoelectronic and steric effects restrict main-chain torsion angles. Replacing proline residues in (ProProGly) 7 collagen strands 4-fluoroproline 4-methylproline leads the most stable known triple helices, having T m values are increased > 50 °C. Differential scanning calorimetry data indicate an entropic basis...
Significance Medium-sized peptides that bind tightly to a specific partner protein can be biomedically useful. However, conventional peptides, comprised exclusively of the 20 proteinogenic α-amino acid residues, are rapidly degraded in vivo by protease enzymes. We have developed strategy delivers protein-binding contain β-amino residues addition α-residues. The unnatural “α/β-peptide” backbone substantially diminishes susceptibility proteolytic degradation relative peptides. Starting from...
Bacterial infections targeting the bloodstream lead to a wide array of devastating diseases such as septic shock and meningitis. To study this crucial type infection, its specific environment needs be taken into account, in particular mechanical forces generated by blood flow. In previous using Neisseria meningitidis model, we observed that bacterial microcolonies forming on endothelial cell surface vessel lumen are remarkably resistant stress. The present aims identify molecular basis...
Type IV pili (Tfp) are widespread filamentous bacterial organelles that mediate multiple virulence-related phenotypes. They composed mainly of pilin subunits, which processed before filament assembly by dedicated prepilin peptidases. Other proteins these peptidases, whose molecular nature and mode action remain enigmatic, play critical roles in Tfp biology. We have performed a detailed structure/function analysis one such protein, PilX from Neisseria meningitidis, is crucial for formation...
D-Glucose/D-Galactose-binding protein (GGBP) mediates chemotaxis toward and active transport of glucose galactose in a number bacterial species. GGBP, like other periplasmic binding proteins, can exist open (ligand-free) closed (ligand-bound) states. We report 0.92 angstroms resolution structure GGBP from Escherichia coli the glucose-bound state first an open, unbound form (at 1.55 resolution). These structures vary angle between two structural domains; observed difference 31 degrees arises...
Pili, which are assembled from protein subunits called pilin, indispensable for the adhesion of capsulated Neisseria meningitidis (MC) to eukaryotic cells. Both MC and gonorrhoeae (GC) pilins glycosylated, but effect this modification is unknown. In GC, a galactose alpha-1,3-N-acetyl glucosamine O-linked Ser-63, whereas in MC, an trisaccharide present between residues 45 73 pilin. As Ser-63 was found be conserved pilin variants different strains, it replaced by Ala two test possible role...
Boronic acids have been typecast as moieties for covalent complexation and are employed only rarely agents non-covalent recognition. By exploiting the profuse ability of a boronic acid group to form hydrogen bonds, we developed an inhibitor HIV-1 protease with extraordinary affinity. Specifically, find that replacing aniline moiety in darunavir phenylboronic leads 20-fold greater affinity protease. X-ray crystallography demonstrates participates three more than amino or any other analog....
In host-associated bacteria, surface and secreted proteins mediate acquisition of nutrients, interactions with host cells, specificity tissue localization. Gram-negative the mechanism by which many cross and/or become tethered to outer membrane remains unclear. The domain unknown function 560 (DUF560) occurs in throughout Proteobacteria has been implicated host-bacterium lipoprotein exposure. We used sequence similarity networking reveal three subfamilies DUF560 homologs. One subfamily...