A5069886641- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Computational Drug Discovery Methods
- ATP Synthase and ATPases Research
- Diabetes Management and Research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Click Chemistry and Applications
- Metal complexes synthesis and properties
- Redox biology and oxidative stress
- Chemical Synthesis and Analysis
- Immune cells in cancer
- Pancreatic function and diabetes
- Enzyme Structure and Function
- Advanced Fluorescence Microscopy Techniques
- Autophagy in Disease and Therapy
- Cytomegalovirus and herpesvirus research
- Lysosomal Storage Disorders Research
- Mass Spectrometry Techniques and Applications
- Parkinson's Disease Mechanisms and Treatments
Charles University
2019-2024
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2017-2024
Rhomboid intramembrane serine proteases have been implicated in several pathologies, and emerge as attractive pharmacological target candidates. The most potent selective rhomboid inhibitors available to date are peptidyl α-ketoamides, but their selectivity for diverse strategies modulate it relevant contexts poorly understood. This gap, together with the lack of suitable vitro models, hinders ketoamide development eukaryotic enzymes. Here we explore structure-activity relationship...
The mitochondrial rhomboid protease PARL regulates mitophagy by balancing intramembrane proteolysis of PINK1 and PGAM5. It has been implicated in the pathogenesis Parkinson's disease, but its investigation as a possible therapeutic target is challenging this context because genetic deficiency may result compensatory mechanisms. To address problem, we undertook hitherto unavailable chemical biology strategy. We developed potent PARL-targeting ketoamide inhibitors investigated effects acute...
Abstract Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. receptors have weak affinities to their ligands; therefore, setting up comprehensive model of NKR-P1-LLT1 interactions that considers state on surface is necessary understand its functions. Here we report crystal structures NKR-P1 NKR-P1:LLT1 complexes, which provides evidence forms homodimers an unexpected...
Nonenzymatic oxidative processes in living organisms are among the inevitable consequences of respiration and environmental conditions. These can lead to formation two stereoisomers (R S) methionine sulfoxide, redox balance between sulfoxide proteins has profound implications on their function. Methionine oxidation be reverted enzymatically by reductases (Msrs). The enzyme classes known fulfill this role MsrA, reducing (S)-isomer, MsrB, (R)-isomer sulfoxide. They strictly stereoselective...
Abstract Working at the border between innate and adaptive immunity, natural killer (NK) cells play a key role in immune system by protecting healthy eliminating malignantly transformed, stressed or virally infected cells. NK cell recognition of target is mediated receptor “zipper” consisting various activating inhibitory receptors, including C-type lectin-like receptors. Among this major group two largest rodent families are NKR-P1 Clr families. Although these have been shown to encode...
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Abstract Human NKR-P1 (CD161, KLRB1 ) and its ligand LLT1 ( CLEC2D are a prototypical inhibitory C-type lectin-like receptor:ligand pair of NK cells with critical role in homing lymphocytes to immune-privileged sites, particularly multiple sclerosis, rheumatoid arthritis, Crohn’s disease. Furthermore, NKR-P1:LLT1 signaling is associated glioblastoma, non-Hodgkin’s lymphoma, breast, prostate cancer. However, the lack structural data on formation complex limits our understanding this...
Abstract Many membrane proteins are thought to function as oligomers, but measuring protein dimerization in native lipid membranes is particularly challenging. Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS) non-invasive, optical methods of choice that have been applied the analysis single-spanning proteins. The effects inherent such two-dimensional systems, excluded volume polytopic transmembrane proteins, proximity FRET, rotational diffusion...