A5072467973- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- SARS-CoV-2 and COVID-19 Research
- Melanoma and MAPK Pathways
- Adenosine and Purinergic Signaling
- Ion channel regulation and function
- Computational Drug Discovery Methods
- Freedom of Expression and Defamation
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Protein Tyrosine Phosphatases
- interferon and immune responses
- 14-3-3 protein interactions
- bioluminescence and chemiluminescence research
- Copyright and Intellectual Property
- Metal complexes synthesis and properties
- Cellular transport and secretion
- Erythrocyte Function and Pathophysiology
- Cancer-related Molecular Pathways
- Calcium signaling and nucleotide metabolism
Vanderbilt University
2024
University of California, Berkeley
2021-2022
Howard Hughes Medical Institute
2022
QB3
2021
Universidad del Noreste
2019
Northeastern University
2015-2019
Institute of Literary Research
2003
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as membrane fusion step entry into host cell. One antiviral class includes peptide inhibitors, which block formation...
Clamp loaders are AAA+ ATPases that load sliding clamps onto DNA. We mapped the mutational sensitivity of T4 bacteriophage clamp and loader by deep mutagenesis, found residues not involved in catalysis or binding display remarkable tolerance to mutation. An exception is a glutamine residue module (Gln 118) located at catalytic interfacial site. Gln 118 forms hydrogen-bonded junction helical unit we term central coupler, because it connects centers DNA clamp. A suppressor mutation indicates...
Water and ligand binding play critical roles in the structure function of proteins, yet their sites significance are difficult to predict a priori. Multiple solvent crystal structures (MSCS) is method where several X-ray solved, each unique environment, with organic molecules that serve as probes protein surface for evolved bind ligands, while first hydration shell essentially maintained. When superimposed, these contain vast amount information regarding hot spots protein-protein or...
The Ras GTPase superfamily of proteins coordinates a diverse set cellular outcomes, including cell morphology, vesicle transport, and proliferation. Primary amino acid sequence analysis has identified Specificity determinant positions (SDPs) that drive diversified functions specific to the Ras, Rho, Rab, Arf subfamilies (Rojas et al . 2012, J Cell Biol 196 :189–201). inclusion water molecules in structural functional adaptation is likely be major response selection pressures evolution, yet...
Ca2+-CaM extracts KRas4B from the plasma membrane, suggesting that KRas4B–CaM interaction plays a role in regulating Ras signaling. To gain mechanistic insight, we provide computational model, supported by experimental structural data, of farnesylated/methylated KRas4B1-185-GTP interacting with CaM solution and at anionic membranes including signaling lipids. Due to multiple modes, observe diverse conformational ensembles complex. A highly populated conformation reveals catalytic domain...
Ras GTPases belong to a subfamily of signal transduction switches found in the superfamily. Three isoforms (H‐, K‐, and N‐Ras) are expressed regulate cellular proliferation, growth, apoptosis. Unregulated activity these proteins is closely related disease, particularly growth tumors.1 The GTP/GDP cycle common regulatory feature signaling output across GTPases. Exchange GDP for GTP within active site results an cascade. GAPs accelerate hydrolysis GDP, turning off signal. In addition exchange...
The Ras superfamily of GTPases is a family binary molecular switches that regulate variety cellular processes, such as proliferation and morphological control. Many members the are localized to membrane environments interact with effectors promote unique signaling consequences. Due strong correlation cancer, structural, biophysical, functional relationships subfamily have been extensively studied. In particular, our work has identified functionally‐related networks allosteric communication...
Abstract Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as membrane fusion step entry into host cell. One antiviral class includes peptide inhibitors which block formation...
H-Ras is a monomeric G-protein that bound to the inner plasma membrane of cell. The intimate interaction formed between protein and plays an important role in its structural functional properties such as activation/inactivation through GTPase activity. This study tests hypothesis conserved helix 5 water-mediated network acts link two distant regions protein1. Two residues within mediate interactions with water molecules were mutated using site-directed mutagenesis: D154A T158A. mutants...
The Ras superfamily of GTPases is a family monomeric molecular switches that regulate variety cellular processes, such as proliferation, migration, trafficking and vesicle formation. Subfamily classification includes Ras, Rho, Ran, Rab, Arf/Sar. While the core structure each small GTPase conserved, subfamily interacts with unique effectors contribute to differing pathway regulation in cell. GTP/GDP cycle common regulatory feature signaling output across GTPases. GTP-bound protein results an...
ABSTRACT Clamp loaders are AAA+ ATPases that load sliding clamps onto DNA. We mapped the mutational sensitivity of T4 bacteriophage clamp and loader by deep mutagenesis, found residues not involved in catalysis or binding display remarkable tolerance to mutation. An exception is a glutamine residue module (Gln 118) located at catalytic interfacial site. Gln 118 forms hydrogen-bonded junction helical unit we term central coupler, because it connects centers DNA clamp. A suppressor mutation...
KRas4B (henceforth called KRas) is a small GTPase that regulates activation of variety signaling pathways, including the Raf/MEK/ERK pathway, leading to cell proliferation, survival, and differentiation. Activation these pathways dependent on nucleotide-bound state KRas: GTP-bound KRas “turns on” while GDP-bound off” signaling. Interestingly, only one three Ras isoforms interacts with Ca2+-bound calmodulin (CaM). However, attempts crystallize KRas/CaM complex have proven difficult due...