Aleksandra Usenik
A5062759078- Clostridium difficile and Clostridium perfringens research
- SARS-CoV-2 and COVID-19 Research
- Antimicrobial Peptides and Activities
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Enzyme Production and Characterization
- Venomous Animal Envenomation and Studies
- Calpain Protease Function and Regulation
- Plant-Microbe Interactions and Immunity
- Antimicrobial Resistance in Staphylococcus
- Carbohydrate Chemistry and Synthesis
- Machine Learning in Bioinformatics
- Bacterial Infections and Vaccines
- interferon and immune responses
- Studies on Chitinases and Chitosanases
- Peptidase Inhibition and Analysis
- Enterobacteriaceae and Cronobacter Research
- NF-κB Signaling Pathways
- Antibiotic Resistance in Bacteria
- Toxin Mechanisms and Immunotoxins
- Plant Stress Responses and Tolerance
- RNA and protein synthesis mechanisms
- Synthesis and biological activity
- Glycogen Storage Diseases and Myoclonus
- Protease and Inhibitor Mechanisms
Jožef Stefan Institute
2017-2024
Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins
2020-2024
National Institute of Chemistry
2010
The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug available to directly treat the disease. In a search for against COVID-19, we have performed high-throughput x-ray crystallographic screen of two repurposing libraries main protease (M
Emerging RNA viruses, including SARS-CoV-2, continue to be a major threat. Cell entry of SARS-CoV-2 particles via the endosomal pathway involves cysteine cathepsins. Due ubiquitous expression, cathepsin L (CatL) is considered promising drug target in context different viral and lysosome-related diseases. We characterized anti-SARS-CoV-2 activity set carbonyl- succinyl epoxide-based inhibitors, which were previously identified as inhibitors cathepsins or related proteases. Calpain inhibitor...
As an important part of metabolism, metabolic flux through the glycolytic pathway is tightly regulated. The most complex control exerted on 6-phosphofructo-1-kinase (PFK1) level; this overrules regulatory role other allosteric enzymes. Among effectors, citrate has been reported to play a vital in suppression enzyme's activity. In eukaryotes, amino acid residues forming binding site for are found both N- and C-terminal region enzyme. These evolved from phosphoenolpyruvate/ADP bacterial PFK1...
Several drug screening campaigns identified Calpeptin as a candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at second target. Indeed, we show that is an extremely potent cysteine cathepsin inhibitor, finding additionally supported by X-ray crystallography. Cell infection proved Calpeptin's efficacy Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated dose 1 mg/kg body weight...
Abstract The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug available to directly treat the prevent virus spreading. In a search against COVID-19, we have performed massive X-ray crystallographic screen of two repurposing libraries main protease (M pro ), which essential replication and, thus, potent target. contrast commonly applied fragment screening experiments with molecules low...
Meningococcal glycoconjugate vaccines sourced from capsular polysaccharides (CPSs) of pathogenic Neisseria meningitidis strains are well-established measures to prevent meningococcal disease. However, the exact structural factors responsible for antibody recognition not known. CPSs serogroups Y and W differ by a single stereochemical center, yet they evoke specific immune responses. Herein, we developed monoclonal antibodies (mAbs) targeting C, Y, evaluated their ability kill bacteria. We...
To achieve productive binding, enzymes and substrates must align their geometries to complement each other along an entire substrate binding site, which may require enzyme flexibility. In pursuit of novel drug targets for the human pathogen S. aureus, we studied peptidoglycan N-acetylglucosaminidases, whose structures are composed two domains forming a V-shaped active site cleft. Combined insights from crystal supported by site-directed mutagenesis, modeling, molecular dynamics enabled us...
TGA (TGACG-binding) transcription factors, which bind their target DNA through a conserved basic region leucine zipper (bZIP) domain, are vital regulators of gene expression in salicylic acid (SA)-mediated plant immunity. Here, we investigated the role StTGA2.1, potato (Solanum tuberosum) lacking full bZIP, named mini-TGA. Such truncated proteins have been widely assigned as loss-of-function mutants. We, however, confirmed that StTGA2.1 overexpression compensates for SA-deficiency,...
Abstract Several drug screening campaigns identified Calpeptin as a candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at second target. Indeed, we show that is an extremely potent cysteine cathepsin inhibitor, finding additionally supported by X-ray crystallography. Cell infection proved Calpeptin’s efficacy Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated dose 1 mg/kg body...
SecA protein is a major component of the general bacterial secretory system. It an ATPase that couples nucleotide hydrolysis to translocation. In some Gram-positive pathogens, second paralogue, SecA2, exports different set substrates, usually virulence factors. To identify SecA2 features from SecA(1)s, we determined crystal structure Clostridioides difficile, important nosocomial pathogen, in apo and ATP-γ-S-bound form. The reveals closed monomer lacking C-terminal tail (CTT) with otherwise...
Abstract Emerging RNA viruses including SARS-CoV-2 continue to be a major threat around the globe. The cell entry of particles via endosomal pathway involves cysteine protease cathepsin L (CatL) among other proteases. CatL is rendered as promising drug target in context different viral and lysosome-related diseases. Hence, discovery structure-based optimization inhibitors high pharmaceutical interest. We herein verified compared anti-SARS-CoV-2 activity set carbonyl succinyl-epoxide-based...
Bacterial cell wall enables the to withstand osmotic pressure and thus its survival in a large set of different habitats.Yet for cells grow divide it has be remodeled controlled manner.Cell is composed glycan strands comprising alternating N-acetylglucosamine (NAG) N-acetylmuramic acid (NAM) cross-linked by peptides.Peptidoglycan hydrolases have been shown important peptidoglycan maturation, turnover recycling as well antibiotic resistance.Bacterial N-acetylglucosaminidases typical...
ABSTRACT TGA transcription factors, which bind their target DNA through a conserved basic region leucine zipper (bZIP) domain, are vital regulators of gene expression in salicylic acid (SA)-mediated plant immunity. Here, we investigate the role StTGA2.1, potato lacking full bZIP, name mini-TGA. Such truncated proteins have been widely assigned as loss-of-function mutants. We, however, confirm that StTGA2.1 overexpression compensates for SA-deficiency. To understand underlying mechanisms,...