A5045006102- Chemokine receptors and signaling
- HER2/EGFR in Cancer Research
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Conservation, Biodiversity, and Resource Management
- Receptor Mechanisms and Signaling
- Enzyme Production and Characterization
- Cancer-related gene regulation
- Glycosylation and Glycoproteins Research
- DNA and Nucleic Acid Chemistry
- Primate Behavior and Ecology
- Phytochemical compounds biological activities
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- DNA Repair Mechanisms
- vaccines and immunoinformatics approaches
- Wnt/β-catenin signaling in development and cancer
- Prostate Cancer Treatment and Research
- Wildlife Ecology and Conservation
- Plant-Derived Bioactive Compounds
Nanyang Technological University
2022
University of South Florida
2012-2019
Florida College
2015
Ligand binding can change the pKa of protein residues and influence enzyme catalysis. Herein, we report three ultrahigh resolution X-ray crystal structures CTX-M β-lactamase, directly visualizing protonation state changes along enzymatic pathway: apo at 0.79 Å, precovalent complex with nonelectrophilic ligand 0.89 acylation transition (TS) analogue 0.84 Å. Binding noncovalent induces a proton transfer from catalytic Ser70 to negatively charged Glu166, formation low-barrier hydrogen bond...
The emergence of CTX-M class A extended-spectrum β-lactamases poses a serious health threat to the public. We have applied structure-based design improve potency novel noncovalent tetrazole-containing inhibitor (Ki = 21 μM) more than 200-fold via structural modifications targeting two binding hot spots, hydrophobic shelf formed by Pro167 and polar site anchored Asp240. Functional groups contacting each spot independently in initial designs were later combined produce analogues with...
CXCL12 is a human chemokine that recognizes the CXCR4 receptor and involved in immune responses metastatic cancer. Interactions between are an important drug target but, like other elongated protein–protein interfaces, present challenges for small molecule ligand discovery due to relatively shallow featureless binding surfaces. Calculations using NMR complex structure revealed hot spot on normally interacts with I4/I6 residues from CXCR4. Virtual screening was performed against model,...
Abstract The lipid A biosynthesis pathway is essential in Pseudomonas aeruginosa . LpxA and LpxD are the first third enzymes this respectively, regarded as promising antibiotic targets. unique structural similarities between these two make them suitable targets for dual-binding inhibitors, a characteristic that would decrease likelihood of mutational resistance increase cell-based activity. We report discovery multiple small molecule ligands bind to P. LpxD, including ligands. Binding poses...
In Gram-negative bacteria, the first step of lipid A biosynthesis is catalyzed by UDP-N-acetylglucosamine acyltransferase (LpxA) through transfer a R-3-hydroxyacyl chain from acyl carrier protein (ACP) to 3-hydroxyl group UDP-GlcNAc. Previous studies suggest that LpxA critical determinant length found in A, which varies among species bacteria. Escherichia coli and Leptospira interrogans, prefers incorporate longer chains (C14 C12, respectively), whereas Pseudomonas aeruginosa, enzyme...
CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis cancer cells. We previously identified small molecule ligands that bind block CXCR4-mediated chemotaxis. now report a 1.9 Å resolution X-ray structure bound by such at site normally sY21 CXCR4. The complex reveals binding hot spots for future inhibitor design suggests new approach targeting CXCL12-CXCR4 signaling in drug discovery.
Casein kinase II (CK2) inhibitors suppress cancer cell growth. In this study, we examined the inhibitory effects of a novel CK2 inhibitor, hematein, on tumor growth in murine xenograft model. We found that lung cells, hematein inhibited growth, Akt/PKB Ser129 phosphorylation, Wnt/TCF pathway and increased apoptosis. model cancer, without significant toxicity to mice tested. Molecular docking showed binds CK2α durable binding sites. Collectively, our results suggest is an allosteric inhibitor...
The chemokine CXCL12 and its G protein-coupled receptor (GPCR) CXCR4 are high-priority clinical targets because of their involvement in metastatic cancers (also implicated autoimmune disease cardiovascular disease). Because chemokines interact with two distinct sites to bind activate receptors, both the GPCRs potential for small molecule inhibition. A number have been validated as drug development, but virtually all discovery efforts focus on GPCRs. However, antagonists exception MSX-122...
Telomeres are protein-DNA complexes that protect the ends of linear eukaryotic chromosomes. Mammalian telomeric DNA consists 5′-(TTAGGG)n-3′ double-stranded repeats, followed by up to several hundred bases a 3′ single-stranded G-rich overhang. The overhang is bound shelterin component POT1 which interacts with TPP1, involved in telomerase recruitment. A previously published crystal structure N-terminal half high affinity ligand 5′-TTAGGGTTAG-3′ showed first six nucleotides, TTAGGG , OB1...
CCL21 chemokine binds the G protein-coupled receptor CCR7, aiding not only in immune response but also cancer metastasis. Compared with other chemokines, has a unique extended unstructured C-terminus that is truncated some naturally occurring variants. We have determined X-ray crystallographic structure of (residues 1-79) lacking and identified, via two-dimensional nuclear magnetic resonance (NMR), putative sulfotyrosine-binding site may recognize such post-translationally modified tyrosine...