A5060104858- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Microbial metabolism and enzyme function
- HIV Research and Treatment
- Microbial bioremediation and biosurfactants
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- DNA and Nucleic Acid Chemistry
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Lipid metabolism and biosynthesis
- Cancer, Lipids, and Metabolism
- Analytical Chemistry and Sensors
- Antimicrobial Resistance in Staphylococcus
- Peptidase Inhibition and Analysis
- Microtubule and mitosis dynamics
- Toxin Mechanisms and Immunotoxins
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Biochemical and Structural Characterization
- Oral and Maxillofacial Pathology
- Bacterial Genetics and Biotechnology
- Peroxisome Proliferator-Activated Receptors
Woodlands Hospital
2020
Duke Medical Center
2012-2018
Duke University
2012-2016
St. Jude Children's Research Hospital
2010-2012
Duke University Hospital
2012
Wake Forest University
2007
Armed Forces Institute of Pathology
2002
In trying to assess the structural integrity of electrospun type II collagen scaffolds, a modified but new technique for cross-linking has been developed. Carbodiimides have previously used cross-link in gels and lyophilized native tissue specimens had not mats until recently. This agent, particular 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), is extreme interest, especially tissue-engineered scaffolds composed specifically polymers (e.g., collagen), because it...
HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of that most likely protective, they not induced current vaccine candidates. In contrast, do neutralize primary strains in TZM-bl infection assay readily by candidates and have also been implicated as secondary correlates decreased risk RV144 efficacy trial. Here, we studied capacity anti-Env...
Immune tolerance mechanisms limit gp41 neutralizing antibody lineage maturation to broadly antibodies.
The type I fatty acid synthase (FASN) is responsible for the de novo synthesis of palmitate. Chain length selection and release performed by C-terminal thioesterase domain (TE1). FASN expression up-regulated in cancer, its activity levels are controlled gene dosage transcriptional post-translational mechanisms. In addition, chain acids produced a II called TE2 (E.C. 3.1.2.14). has been implicated breast cancer generates broad lipid distribution within milk. molecular basis ability to compete...
The 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate synthase (DHPS) enzymes catalyze sequential metabolic reactions in the folate biosynthetic pathway of bacteria lower eukaryotes. Both represent validated targets for development novel anti-microbial therapies. We report herein that genes which encode FtHPPK FtDHPS from biowarfare agent Francisella tularensis are fused into a single polypeptide. potential simultaneously targeting both modules with pterin...
In Gram-negative bacteria, the hydrophobic anchor of outer membrane lipopolysaccharide is lipid A, a saccharolipid that plays key roles in both viability and pathogenicity these organisms. The tetraacyldisaccharide 4′-kinase (LpxK) diverse P-loop–containing nucleoside triphosphate hydrolase superfamily catalyzes sixth step biosynthetic pathway only known P-loop kinase to act upon substrate at membrane. Here, we report crystal structures apo- ADP/Mg 2+ -bound forms Aquifex aeolicus LpxK...
Rotation of the coiled-coil stalk kinesin-14 motors is thought to drive displacements or steps by motor along microtubules, but structural changes that trigger rotation and nucleotide state in which it occurs are not certain. Here we report a neck mutant releases ADP more slowly than wild type shows weaker microtubule affinity, consistent with defective rotation. Unexpectedly, crystal structures show fully rotated – neck-motor interactions destabilize stalk, causing rotate be released alter...
Calcineurin heterodimer, comprised of the catalytic (CnaA) and regulatory (CnaB) subunits, localizes at hyphal tips septa to direct growth, septation, disease in human pathogen Aspergillus fumigatus . Here we discovered a novel motif (FMDVF) required for this critical CnaA septal localization, including residues Phe368, Asp370 Phe372 overlapping cyclosporine A‐cyclophilin A‐binding domain, CnaB‐binding helix FK506‐FKBP12‐binding pocket. Mutations adjacent Asn367, Trp374, Ser375 confer FK506...
The intrinsic <sc>l</sc>-DNA binding properties of a natural DNA polymerase was discovered.
A target with therapeutic potential, lysine‐specific demethylase 1A (KDM1A) is a regulator of gene expression whose tower domain protein–protein interaction motif. This facilitates the KDM1A coregulators and multiprotein complexes that direct its activity to nucleosomes. We describe design characterization chimeric ‘towerless’ KDM1A, termed nΔ150 KDM1AΔTower KDM1B chimera (chKDM1AΔTower), which incorporates region from paralog 1B (KDM1B). copurifies FAD displays activity, but fails bind...
The sixth step in the lipid A biosynthetic pathway involves phosphorylation of tetraacyldisaccharide-1-phosphate (DSMP) intermediate by cytosol-facing inner membrane kinase LpxK, a member P-loop-containing nucleoside triphosphate (NTP) hydrolase superfamily. We report kinetic characterization LpxK from Aquifex aeolicus and crystal structures complex with ATP precatalytic binding state, analogue AMP-PCP closed catalytically competent conformation, chloride anion revealing an inhibitory...
Non-Hodgkin's lymphoma may arise in extranodal tissues within the head and neck region. These lesions occur oral cavity, but rarely appear on gingiva. Due to their malignant nature, rapid identification, diagnosis, treatment of non-Hodgkin's lymphomas are essential patient survival.An unusual case primary is described. The small lesion arose gingiva alveolar mucosa. Upon excision, tissue was submitted for microscopic examination, with expectation that would be benign excision constitute...