A5100460230- Melanoma and MAPK Pathways
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Fungal and yeast genetics research
- Crime Patterns and Interventions
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Axon Guidance and Neuronal Signaling
- Chemical Synthesis and Analysis
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Nerve injury and regeneration
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Crime, Illicit Activities, and Governance
- Chronic Lymphocytic Leukemia Research
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Neurogenesis and neuroplasticity mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Medicinal Plants and Bioactive Compounds
- Fibroblast Growth Factor Research
University of Southern California
2016-2025
Southern California University for Professional Studies
2025
Dezhou University
2024
Cornell University
2020
Louisiana State University Health Sciences Center Shreveport
2019
Second Affiliated Hospital of Jilin University
2019
Plexxikon (United States)
2005-2018
Zunyi Medical University
2018
Liaoning Shihua University
2016
Peking University
2015
BRAF V600E is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting “active” kinases have demonstrated significant utility in therapeutic repertoire against cancer. Therefore, we pursued development of specific B-Raf, and allele particular. By using a structure-guided discovery approach, potent selective inhibitor active B-Raf has been discovered. PLX4720, 7-azaindole derivative that inhibits with an IC 50 13 nM, defines class marked selectivity both...
We estimated effective atomic contact energies (ACE), the desolvation free required to transfer atoms from water a protein's interior, using an adaptation of method introduced by S. Miyazawa and R. L. Jernigan. The were obtained for 18 different atom types, which resolved on basis way their properties cluster in 20 common amino acids. In addition providing information at highest resolution compatible with amount quality data currently available, itself has several new features, including its...
The active sites of 491 human protein kinase domains are highly conserved, which makes the design selective inhibitors a formidable challenge. We used structural bioinformatics approach to identify two selectivity filters, threonine and cysteine, at defined positions in site p90 ribosomal S6 (RSK). A fluoromethylketone inhibitor, designed exploit both potently selectively inactivated RSK1 RSK2 mammalian cells. Kinases with only one filter were resistant yet they became sensitized after...
Meiosis is thought to require the protein kinase Ime2 early for DNA replication and cyclin-dependent Cdc28 late chromosome segregation. To elucidate roles of these kinases, we inhibited their activities using conditional mutants that are sensitive chemical inhibitors. Our studies reveal both have critical in meiotic S phase M phase. Early inhibition analog-sensitive cdc28-as1 blocked replication, revealing a previously undetected role Cdc28. Yet was dispensable one its functions mitotic cell...
One of the principal goals structural genomics initiative is to identify total repertoire protein folds and obtain a global view “protein structure universe.” Here, we present 3D map fold space in which structurally related are represented by spatially adjacent points. Such representation reveals high-level organization that intuitively interpretable. The shape overall distribution defined three dominant trends: secondary class, chain topology, domain size. Random coil-like structures small...
In a search for more effective anti-diabetic treatment, we used process coupling low-affinity biochemical screening with high-throughput co-crystallography in the design of series compounds that selectively modulate activities all three peroxisome proliferator-activated receptors (PPARs), PPARalpha, PPARgamma, and PPARdelta. Transcriptional transactivation assays were to select from this chemical bias toward partial agonism circumvent clinically observed side effects full PPARgamma agonists....
S-phase cyclin-dependent kinase Cdc28–Clb5 (CDK-S) and Dbf4-dependent Cdc7–Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is also essential meiotic recombination because it phosphorylates Ser30 Mer2, a meiosis-specific double-strand break (DSB) protein. This work shows that phosphorylation Mer2 by primes subsequent DDK on Ser29, creating negatively charged “patch” necessary DSB formation. S30 S29 can be bypassed phosphomimetic...
Phosphorylation of the Saccharomyces cerevisiae Snf1 kinase activation loop is determined by integration two reaction rates: rate phosphorylation upstream kinases and dephosphorylation Glc7. The activities Snf1-activating do not appear to be glucose-regulated, since immune complex assays with each three show similar levels activity when prepared from cells grown in either high or low glucose. In contrast, was strongly regulated When de novo inhibited, found stable glucose but rapidly lost...
BRAF is among the most frequently mutated oncogenes in human cancers. Multiple small molecule kinase inhibitors have been approved for treating melanoma carrying BRAF-V600 mutations. However, benefits of are generally short-lived. Small molecule-mediated targeted protein degradation has recently emerged as a novel pharmaceutical strategy to remove disease proteins through hijacking cellular ubiquitin proteasome system (UPS). In this study, we developed thalidomide-based heterobifunctional...