A5015592397- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Antibiotic Resistance in Bacteria
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Microbial Natural Products and Biosynthesis
- Protein Degradation and Inhibitors
- Bacterial Genetics and Biotechnology
- Advanced biosensing and bioanalysis techniques
- Mycobacterium research and diagnosis
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Synthesis and Catalytic Reactions
- Natural Compounds in Disease Treatment
- Cleft Lip and Palate Research
- Polyamine Metabolism and Applications
- Synthesis and biological activity
- Chromatin Remodeling and Cancer
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and properties of polymers
- Antibiotics Pharmacokinetics and Efficacy
Johns Hopkins University
2008-2024
Johns Hopkins Medicine
2008-2024
University of Michigan
2006
Novartis (United States)
2006
SET domain enzymes represent a distinct family of protein lysine methyltransferases in eukaryotes. Recent studies have yielded significant insights into the structural basis substrate recognition and product specificities these enzymes. However, mechanism by which catalyze transfer methyl group from S-adenosyl-l-methionine to ϵ-amine has remained unresolved. To elucidate this mechanism, we determined structures plant enzyme, pea ribulose-1,5 bisphosphate carboxylase/oxygenase large subunit...
SUMMARY While nucleoside DNA methyltransferase inhibitors (DNMTi) such as decitabine and azacitidine are effective in treating myelodysplatic syndrome (MDS)/leukemia, they have had limited utility for the majority of other cancers. Through a chemical library screen, we identified that triptolide, diterpenoid epoxide from Tripterygium wilfordii , or analogs significantly augmented epigenetic anti-cancer effects vitro vivo . These were attributable to inhibition DCTPP1-mediated cleavage...
Exonuclease VII (ExoVII) is a ubiquitous bacterial nuclease. Encoded by the xseA and xseB genes, ExoVII participates in multiple nucleic acid–dependent pathways including processing of multicopy single-stranded DNA repair covalent DNA–protein crosslinks (DPCs). Although many biochemical properties have been defined, little known about its structure/function relationships. Here, we use cryoelectron microscopy (cryoEM) to determine that Escherichia coli comprises highly elongated XseA 4 ·XseB...
The escalating threat posed by antibiotic resistance is a global concern and underscores the need for new antibiotics. In this context, recent discovery of evybactin, nonribosomal depsipeptide that selectively potently inhibits growth M. tuberculosis, particularly noteworthy. Here, we present first total synthesis natural product, along with revision its assigned structure. Our studies revealed disparity between structure originally proposed evybactin actual configuration. Specifically,...
Abstract A new series of nitric oxide‐donating fluoroquinolone/oximes was prepared in this study. The oxide release from the compounds measured using a modified Griess colorimetric method. antitubercular evaluation synthesized indicated that ketone derivatives 2b and 2e oximes 3b 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies molecular modeling Mycobacterium tuberculosis gyrase were pursued to explain observed...
The DEAD-box RNA helicase Ded1, which is essential in yeast and known as DDX3 humans, shuttles between the nucleus cytoplasm takes part several basic processes including processing translation. A key interacting partner of Ded1 exportin Xpo1, together with GTP-bound state small GTPase Ran, facilitates unidirectional transport out nucleus. Here we demonstrate that Xpo1 Ran[GTP] reduce RNA-stimulated ATPase activities Ded1. Binding inhibition by depend on affinity nuclear export sequence (NES)...
ATP‐dependent chromatin remodeling complexes play a central role in the assembly, disassembly, and repositioning of nucleosomes. While reaction is driven by conserved ATPase motor, it not known how this motor regulated auxiliary domains. We have solved crystal structure Chd1 chromodomains coupled to which suggests that negatively regulate motor. In crystal, acidic helical linker between contacts DNA‐binding surface on blocking DNA access Naked poor substrate for ATPase, we find disruption...