A5077521227- Enzyme Structure and Function
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Glycosylation and Glycoproteins Research
- Microbial Metabolic Engineering and Bioproduction
- Electron Spin Resonance Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Magnetism in coordination complexes
- Cancer Research and Treatments
- Microbial Metabolism and Applications
- Pneumocystis jirovecii pneumonia detection and treatment
- Porphyrin Metabolism and Disorders
- Boron Compounds in Chemistry
- Lipid Membrane Structure and Behavior
- Bacterial Genetics and Biotechnology
- HIV/AIDS drug development and treatment
- Alcoholism and Thiamine Deficiency
- Infections and bacterial resistance
- Steroid Chemistry and Biochemistry
- Microbial Natural Products and Biosynthesis
- Melanoma and MAPK Pathways
- Burkholderia infections and melioidosis
- Metalloenzymes and iron-sulfur proteins
- Enzyme Production and Characterization
- Monoclonal and Polyclonal Antibodies Research
Center for Infectious Disease Research
2020-2025
UCB Pharma (United States)
2020-2025
Acceleron Pharma (United States)
2023
Urban College of Boston
2021
Beryllium (United States)
2017-2019
University of Virginia
2010-2013
University of Georgia
2001-2007
University of Alabama at Birmingham
2005
Oak Ridge National Laboratory
2005
Joint Center for Structural Genomics
2005
Posttranslational lipidation provides critical modulation of the functions some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X any residue). Isoprenylation followed by cleavage AAX amino acid and, cases, additional proteolytic cuts. We determined crystal structure protease Ste24p, a zinc metalloprotease catalyzing two steps maturation yeast mating...
The methylerythritol phosphate (MEP) pathway is a metabolic that produces the isoprenoids isopentyl pyrophosphate and dimethylallyl pyrophosphate. Notably, MEP present in bacteria not mammals, which makes enzymes of attractive targets for discovery new anti-infective agents due to reduced chances off-target interactions leading side effects. There are seven pathway, fifth IspF. Crystal structures Burkholderia pseudomallei IspF were determined with five different sulfonamide ligands bound....
Mycobacterium tuberculosis is a Gram-positive bacillus that causes and leading cause of mortality worldwide. This disease growing health threat due to the occurrence multidrug resistance. Mycolic acids are essential for generating cell walls their modification important virulence persistence M. tuberculosis. A family S -adenosylmethionine-dependent mycolic acid synthases modify represent promising drug targets. UmaA currently least-understood member this family. paper describes crystal...
Understanding the structure and dynamics of membrane proteins in their native, hydrophobic environment is important to understanding how these function. EPR spectroscopy combination with site-directed spin labeling (SDSL) can measure native lipid environment; however, until now measured have been qualitative due limited knowledge nitroxide label's intramolecular motion environment. Although several studies elucidated structural origins line shapes water-soluble proteins, spectra spin-labeled...
The Ets-Related Gene (ERG) belongs to the Ets family of transcription factors and is critically important for maintenance hematopoietic stem cell population. A chromosomal translocation observed in majority human prostate cancers leads aberrant overexpression ERG. We have identified regions flanking ERG domain responsible autoinhibition DNA binding solved crystal structures uninhibited, autoinhibited, DNA-bound NMR-based measurements backbone dynamics show that uninhibited undergoes...
Low solubility of proteins overexpressed in E. coli is a frequent problem high-throughput structural genomics. To improve from mesophilic Shewanella oneidensis MR-1 and thermophilic Clostridium thermocellum JW20, an approach was attempted that included fusion the target protein to maltose-binding (MBP) decrease induction temperature. The MBP selected as most efficient solubilizing carrier when compared glutathione S-transferase Nus A protein. tobacco etch virus (TEV) protease recognition...
In this work, electron paramagnetic resonance (EPR) spectroscopy and X-ray crystallography were used to examine the origins of EPR line shapes from spin-labels at protein–lipid interface on β-barrel membrane protein BtuB. Two atomic-resolution structures obtained for methanethiosulfonate spin-label derivatized cysteines membrane-facing surface At one these sites, position 156, label side chain resides in a pocket formed by neighboring residues; however, it extends yields single-component...
Ferrochelatase catalyzes the terminal step in heme biosynthesis, insertion of ferrous iron into protoporphyrin to form protoheme IX. The crystal structures human ferrochelatase both with and without substrate bound have been determined previously. substrate-free enzyme has an open active site pocket, while substrate-bound enzyme, pocket is closed around porphyrin macrocycle a number residues reoriented side chains. To understand how why these structural changes occur, we substituted three...
Using a high degree of automation, the crystallography core at Southeast Collaboratory for Structural Genomics (SECSG) has developed high-throughput protein-to-structure pipeline. Various robots and automation procedures have been adopted integrated into pipeline that is capable screening 40 proteins crystallization solving four protein structures per week. This composed three major units: crystallization, structure determination/validation crystallomics. Coupled with protein-production...
Double electron-electron resonance in conjunction with site-directed spin labeling has been used to probe natural conformational sampling of the human tumor necrosis factor α trimer. We suggest a previously unreported, predeoligomerization conformation trimer that shown be sampled at low frequency. A model this trimeric state constructed based on crystal structures using double-electron-electron-resonance distances. The shows one protomers rotated and tilted outward tip end, leading breaking...
Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide usually present as co-infections. Increasing resistance of Ng to currently recommended dual therapy azithromycin ceftriaxone presents therapeutic challenges for syndromic management Ng-Ct Development a safe, effective, inexpensive co-infections is an effective strategy global control prevention these two prevalent bacterial infections. Glyceraldehyde-3-phosphate...
Clostridium perfringens is a ubiquitous anaerobic bacterium that commonly found not only in soil but also the gastrointestinal tract of higher animals. Its pathogenicity has been reviewed extensively.1-3 As major cause infections humans and animals,4 C. suspected to employ hydrolytic enzymes degradation mucous glycoproteins. A unique endo-β-galactosidase, Endo-β-GalGnGa, capable releasing GlcNAcα1-4Gal from porcine gastric mucin was discovered serendipitously as contaminant commercially...
Abstract Thiamine monophosphate kinase (ThiL) catalyzes the last step of thiamine pyrophosphate (TPP) synthesis, ATP-dependent phosphorylation (TMP) to pyrophosphate. We solved structure ThiL from human pathogen A. baumanii in complex with a pair substrates TMP and non-hydrolyzable adenosine triphosphate analog, products TPP diphosphate. High resolution data anomalous diffraction allows for detailed description binding mode products, their metal environment. The structures further support...
The unique clostridial endo-β-galactosidase (Endo-β-GalGnGa) capable of releasing the disaccharide GlcNAcα1,4Gal from O-glycans expressed in gastric gland mucous cell-type mucin has been crystallized. crystal belongs to space group P63, with unit-cell parameters a = 160.4, c 86.1 Å. Under cryocooled conditions and using synchrotron X-ray source, crystals diffract 1.82 Å resolution. asymmetric unit contains two or three molecules.