A5084202200- Advanced Glycation End Products research
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Protein Structure and Dynamics
- RNA modifications and cancer
- Connexins and lens biology
- Natural Antidiabetic Agents Studies
- Bacterial Genetics and Biotechnology
- Toxin Mechanisms and Immunotoxins
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Phytoplasmas and Hemiptera pathogens
- Diabetes and associated disorders
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Advanced biosensing and bioanalysis techniques
- Antimicrobial Peptides and Activities
- S100 Proteins and Annexins
- Carbohydrate Chemistry and Synthesis
- Advanced NMR Techniques and Applications
- ATP Synthase and ATPases Research
University at Albany, State University of New York
2016-2025
Albany State University
2016-2025
New York University
2024
State University of New York
2018
Albany Research Institute
2013-2018
University of Haifa
2011
New York Structural Biology Center
2002-2008
Rockefeller University
2001-2006
Pennsylvania State University
2002
Belarusian State University
1996
The overexpression of Hdm2 and HdmX is a common mechanism used by many tumor cells to inactive the p53 suppressor pathway promoting cell survival. Targeting has emerged as validated therapeutic strategy for treating cancers with wild-type p53. Small linear peptides mimicking N-terminal fragment have been shown be potent Hdm2/HdmX antagonists. potential use these peptides, however, limited their poor stability bioavailability. Here, we report engineering cyclotide MCoTI-I efficiently...
The receptor for advanced glycated end products (RAGE) is a multiligand that implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. ability RAGE to recognize (AGEs) formed by nonenzymatic glycoxidation cellular proteins places category pattern recognition receptors. structural mechanism AGE was an enigma due diversity chemical structures found AGE-modified proteins. Here, using NMR spectroscopy we showed...
Diabetes-induced hyperglycemia increases the extracellular concentration of methylglyoxal. Methylglyoxal-derived hydroimidazolones (MG-H) form advanced glycation end products (AGEs) that accumulate in serum diabetic patients. The binding hydroimidozolones to receptor for AGEs (RAGE) results long-term complications diabetes typified by vascular and neuronal injury. Here we show methylglyoxal-modified albumin RAGE signal transduction. Chemically synthesized peptides containing bind...
Herein, we report for the first time design and synthesis of a novel cyclotide able to efficiently inhibit HIV-1 viral replication by selectively targeting cytokine receptor CXCR4. This was accomplished grafting series topologically modified CVX15 based peptides onto loop 6 MCoTI-I. The most active compound produced in this study potent CXCR4 antagonist (EC50 ≈ 20 nM) an efficient cell-entry blocker 2 nM). also showed high stability human serum, thereby providing promising lead type...
Abstract The receptor for advanced glycation endproducts (RAGE) binds diverse ligands linked to chronic inflammation and disease. NMR spectroscopy x-ray crystallization studies of the extracellular domains RAGE indicate that bind by distinct charge- hydrophobicity-dependent mechanisms. cytoplasmic tail (ct) is essential ligand-mediated signal transduction consequent modulation gene expression cellular properties. signaling requires interaction ctRAGE with intracellular effector, mammalian...
Protein splicing is a posttranslational autocatalytic process in which an intervening sequence, termed intein, removed from host protein, the extein. Although we have reasonable picture of basic chemical steps protein splicing, our knowledge how these are catalyzed and regulated less well developed. In current study, combination NMR spectroscopy segmental isotopic labeling has been used to study structure active precursor, corresponding N-extein fusion Mxe GyrA intein. The 1 J NC′ coupling...
Abstract Background Human S100A12 is a member of the S100 family EF-hand calcium-modulated proteins that are associated with many diseases including cancer, chronic inflammation and neurological disorders. an important factor in host/parasite defenses inflammatory response. Like several other proteins, it binds zinc copper addition to calcium. Mechanisms regulation have been proposed for number e.g. S100B, S100A2, S100A7, S100A8/9. The interaction their targets strongly dependent on cellular...
The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule that plays central role in the etiology of diabetes complications, inflammation, and neurodegeneration. cytoplasmic domain RAGE (C-terminal RAGE; ctRAGE) critical RAGE-dependent signal transduction. As most membrane-proximal event, mDia1 binds to ctRAGE, it essential ligand-stimulated phosphorylation AKT proliferation/migration. We show ctRAGE contains an unusual α-turn mediates mDia1-ctRAGE...
Perfect circle. We report the biosynthesis of a natively folded cyclotide, MCoTI-II, in E. coli by intracellular backbone cyclization linear cyclotide–intein fusion precursor. The cyclized peptide then spontaneously folds into its native conformation. Biosynthetic access to correctly cyclotides allows possibility generating cell-based combinatorial libraries that can be screened, inside living cells, for their ability modulate or inhibit cellular processes. Supporting information this...
Abstract Background Spartin protein is involved in degradation of epidermal growth factor receptor and turnover lipid droplets a lack expression this responsible for hereditary spastic paraplegia type 20 (SPG20). multifunctional that associates with many cellular organelles, including droplets. Recent studies showed spartin interacts E3 ubiquitin ligases belong to the neural precursor cell-expressed developmentally downregulated gene (Nedd4) family, atrophin-1-interacting 4 (AIP4/ITCH)....
In-cell NMR in the yeast Pichia pastoris was used to study influence of metabolic changes on protein structure and dynamics at atomic resolution. Induction ubiquitin overexpression from methanol induced AOX1 promoter results being localized cytosol yields a well-resolved in-cell spectrum. When P. is grown mixed carbon source containing both dextrose methanol, found small storage vesicles distributed cytosol, resulting spectrum broadened. The sequestration overexpressed proteins into...
Amyloid fibrils are β-sheet-rich protein aggregates commonly found in the organs and tissues of patients with various amyloid-associated diseases. Understanding structural organization amyloid can be beneficial for search drugs to successfully treat diseases associated misfolding. The structure insulin was characterized by deep ultraviolet resonance Raman (DUVRR) Nuclear Magnetic Resonance (NMR) spectroscopy combined hydrogen-deuterium exchange. compositions fibril core unordered parts were...
Historically introduced by McConkey to explain the slow mutation rate of highly abundant proteins, weak protein (quinary) interactions are an emergent property living cells. The complexes that result from quinary transient and thus difficult study biochemically in vitro. Cross-correlated relaxation-induced polarization transfer-based in-cell nuclear magnetic resonance allows characterization with atomic resolution inside live prokaryotic eukaryotic We show RNAs important component...
Small-molecule antagonism of RAGE-DIAPH1 reduces diabetes-related complications in mice.
Bacterial σ factors combine with the catalytic core RNA polymerase to direct process of transcription initiation through sequence-specific interactions −10 and −35 elements promoter DNA. In absence polymerase, DNA-binding function is autoinhibited by its own N-terminal 90 amino acids (region 1.1), putatively a interaction conserved region 4.2, which binds element. present work, this mechanism autoinhibition was studied using combination NMR spectroscopy segmental isotopic labeling 70 -like...
Cell-ing point: This study shows that MCoTI-cyclotides can provide an ideal scaffold for the biosynthesis of large combinatorial libraries inside living E. coli cells. Coupled to appropriate in vivo reporter system, this library may rapidly be screened, example, by fluorescence-activated cell sorting. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted authors....
We developed an in-cell NMR assay for screening small molecule interactor libraries (SMILI-NMR) compounds capable of disrupting or enhancing specific interactions between two more components a biomolecular complex. The method relies on the formation well-defined biocomplex and utilizes spectroscopy to identify molecular surfaces involved in interaction at atomic scale resolution. Changes surface caused by interfering with complex are used as read-out assay. nature experimental protocol...