A5009199404- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Adenosine and Purinergic Signaling
- Estrogen and related hormone effects
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- Mass Spectrometry Techniques and Applications
- Sphingolipid Metabolism and Signaling
- Fluorine in Organic Chemistry
- S100 Proteins and Annexins
- Advanced Electron Microscopy Techniques and Applications
- Asthma and respiratory diseases
- Immune Response and Inflammation
- Steroid Chemistry and Biochemistry
- Cholesterol and Lipid Metabolism
- Protein Structure and Dynamics
- Bioactive Compounds and Antitumor Agents
- Viral Infectious Diseases and Gene Expression in Insects
- Nanoplatforms for cancer theranostics
- Mast cells and histamine
- NF-κB Signaling Pathways
Moscow Institute of Physics and Technology
2016-2024
Moscow Power Engineering Institute
2021
International Medical Research (Germany)
2019
Research & Development Corporation
2019
Two distinct antagonist-bound structures of CysLT 1 R reveal unique ligand-binding modes and signaling mechanisms.
Abstract The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. Single-molecule Förster Resonance Energy Transfer (smFRET) well suited to quantify dynamics for individual protein molecules; however, its application GPCRs challenging. Therefore, smFRET has been limited studies inter-receptor interactions in cellular membranes and detergent environments. Here, we performed experiments on functionally active human A 2A adenosine...
Abstract Cysteinyl leukotriene G protein-coupled receptors CysLT 1 and 2 regulate pro-inflammatory responses associated with allergic disorders. While selective inhibition of R has been used for treating asthma diseases over two decades, recently started to emerge as a potential drug target against atopic asthma, brain injury central nervous system disorders, well several types cancer. Here, we describe four crystal structures in complex three dual R/CysLT antagonists. The reported together...
Cysteinyl leukotriene G protein-coupled receptors, CysLT1R and CysLT2R, regulate bronchoconstrictive pro-inflammatory effects play a key role in allergic disorders, cardiovascular diseases, cancer. antagonists have been widely used to treat asthma while CysLT2R is potential target against uveal melanoma. However, very few selective antagonist chemotypes for CysLT receptors are available, the design of such ligands has proved be challenging. To overcome this obstacle, we took advantage...
The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PRs) - S1P1-5. S1P5 is predominantly expressed in nervous and immune systems, regulating the egress natural killer cells from lymph nodes playing a role neurodegenerative disorders, as well carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads side effects. In this article, we...
Abstract Toll-like receptors (TLRs) play an important role in the innate immune response. While a lot is known about structures of their extracellular parts, many questions are still left unanswered, when structural basis TLR activation analyzed for intracellular domains. Here we report structure and dynamics TLR1 toll-interleukin like (TIR) cytoplasmic domain crystal solution. We found that TLR1-TIR capable specific binding Zn with nanomolar affinity. Interactions mediated by cysteine...
Abstract Structural studies of challenging targets such as G protein-coupled receptors (GPCRs) have accelerated during the last several years due to development new approaches, including small-wedge and serial crystallography. Here, we describe deposition seven datasets consisting X-ray diffraction images acquired from lipidic cubic phase (LCP) grown microcrystals two human GPCRs, Cysteinyl leukotriene 1 2 (CysLT R CysLT R), in complex with various antagonists. Five were collected using...
G protein-coupled Receptors (G Receptors, GPCRs) play a key role in the transmission of extracellular signals and regulation many biological processes, which makes these membrane proteins one most important classes targets for pharmacological agents. The significant increase number atomic structures GPCRs recently has paved way Structure Based Drug Design (SBDD). SBDD uses information on structure receptor-ligand complex to search affinity selective ligands without need high-throughput...
G protein-coupled receptors (GPCRs) are transmembrane proteins that participate in most physiological processes and serve as key pharmacological targets. Recent advances structural biology of GPCRs have enabled the development drugs based on structure (Structure Based Drug Design, SBDD). SBDD utilizes information about receptor– ligand complex to search for suitable compounds, expanding chemical space without need experimental screening. In our review we include a description Structural-base...
Abstract Mycobacterium tuberculosis (Mtb) infection is among top ten causes of death worldwide, and the number drug-resistant strains increasing. The direct interception human immune signaling molecules by Mtb remains elusive, limiting drug discovery. Oxysterols secosteroids regulate both innate adaptive responses. Here we report a functional, structural, bioinformatics study enzymes initiating cholesterol catabolism demonstrated their interrelation with immunity. We show that these...
Abstract The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. Single-molecule Förster Resonance Energy Transfer (smFRET) well-suited to quantify dynamics for individual protein molecules, however, its application GPCRs challenging; therefore, smFRET has been limited studies interreceptor interactions in cellular membranes and detergent environments. Here, we performed experiments on functionally active human A 2A adenosine...
ABSTRACT The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PR) - 1-5 . 5 is predominantly expressed in nervous and immune systems, regulating the egress natural killer cells from lymph nodes playing a role neurodegenerative disorders, as well carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads side effects. In this article, we...