A5037044774- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Lysosomal Storage Disorders Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Enzyme Structure and Function
- Rabies epidemiology and control
- Trypanosoma species research and implications
- Bacterial Genetics and Biotechnology
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- Leptospirosis research and findings
- Cellular transport and secretion
- Bacillus and Francisella bacterial research
- Cancer, Hypoxia, and Metabolism
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Pharmacological Effects of Natural Compounds
- Bioactive Compounds and Antitumor Agents
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Diet, Metabolism, and Disease
- Calcium signaling and nucleotide metabolism
- Veterinary medicine and infectious diseases
Graz University of Technology
2016-2024
Institut Pasteur
2013-2023
Centre National de la Recherche Scientifique
2013-2023
Université Paris Cité
2022
Biobase (Germany)
2021
Institute of Organic Chemistry
2015-2018
Laboratoire de Cristallographie et RMN Biologiques
2013
Jazz Pharmaceuticals (United States)
2008
World Health Organization - Pakistan
2007
U.S. Dairy Forage Research Center
2006
Significance We report the identification of a cubane-modified aptamer (cubamer) against malaria biomarker Plasmodium vivax lactate dehydrogenase (PvLDH). The cubamer contains benzene isostere cubane, which is entirely alien to biology. crystal structure cubamer–protein complex reveals binding mechanism involving formation an unprecedented cubane pocket and unusual C–H⋅⋅⋅O hydrogen bond. Importantly, capable distinguishing PvLDH from falciparum LDH despite very high sequence homology,...
Abstract: Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X‐ray crystal structure N ‐acetyl serotonin methyltransferase (ASMT), last enzyme biosynthesis pathway. The polypeptide chain ASMT consists C‐terminal domain, which typical other SAM‐dependent O ‐methyltransferases, an N‐terminal intertwines several helices another monomer form...
Calmodulin (CaM) is an evolutionarily conserved eukaryotic multifunctional protein that functions as the major sensor of intracellular calcium signaling. Its calcium-modulated function regulates activity numerous effector proteins involved in a variety physiological processes diverse organs, from proliferation and apoptosis, to memory immune responses. Due pleiotropic roles CaM normal pathological cell functions, antagonists are needed for fundamental studies well potential therapeutic...
Pathogenic Leptospira spp. are the agents of leptospirosis, an emerging zoonotic disease. Analyses genomes have shown that pathogenic leptospires (but not saprophytes) possess a large number genes encoding proteins containing leucine-rich repeat (LRR) domains. In other bacteria, with LRR domains been to be involved in mediating host-cell attachment and invasion, but their functions remain unknown Leptospira. To gain insight into potential function leptospiral proteins, crystal structures...
Abstract The molecular mechanisms and forces involved in the translocation of bacterial toxins into host cells are still a matter intense research. adenylate cyclase (CyaA) toxin from Bordetella pertussis displays unique intoxication pathway which its catalytic domain is directly translocated across target cell membranes. CyaA region contains segment, P454 (residues 454–484), exhibits membrane‐active properties related to antimicrobial peptides. Herein, results show that this peptide able...
Rap1 is an essential DNA-binding factor from the yeast Saccharomyces cerevisiae involved in transcription and telomere maintenance. Its binding to DNA targets at particular loci, may optimize its ability form functional macromolecular assemblies. It a modular protein, rich large potentially unfolded regions, comprising BRCT, Myb RCT well-structured domains. Here, we present architectures of Rap1/DNA complex, built through step-by-step integration small angle X-ray scattering, crystallography...
Both epidemiological and experimental data indicate that a diet rich in fiber may reduce cancer risk. One possible mechanism is by adsorbing carcinogens transporting them out of the body without metabolic activation. We investigated role lignification feruloylation on adsorption four most relevant heterocyclic aromatic amines food: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP),...
Rv1098c and bind by X‐ray crystallography ( View interaction )
Arylamine N-acetyltransferases (NATs), a class of xenobiotic-metabolizing enzymes, catalyze the acetylation aromatic amine compounds through strictly conserved Cys-His-Asp catalytic triad. Each residue is essential for catalysis in both prokaryotic and eukaryotic NATs. Indeed, (HUMAN)NAT2 variants, mutation Asp to Asn, Gln, or Glu dramatically impairs enzyme activity. However, putative atypical NAT harboring triad was recently identified Bacillus cereus ((BACCR)NAT3) but has not yet been...
The vancomycin-resistant Staphylococcus aureus VRSA-9 clinical isolate was partially dependent on glycopeptide for growth. responsible vanA operon had the same organization as that of Tn1546 and located a plasmid. chromosomal D-Ala:D-Ala ligase (ddl) gene two point mutations led to Q260K A283E substitutions, resulting in 200-fold decrease enzymatic activity compared wild-type strain VRSA-6. To gain insight into mechanism enzyme impairment, we determined crystal structure Ddl showed mutation...
We developed potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-β-D-glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over HexB. It non-toxic increased protein O-GlcNAcylation the culture murine neural cells, showing new alternatives treatment tauopathies.
A new class of compounds inhibiting de-O-glycosylation proteins has been identified. Highly substituted diaminocyclopentanes are impressively selective reversible non-transition state O-β-N-acetyl-d-glucosaminidase (O-GlcNAcase) inhibitors. The ease preparative access and remarkable biological activities provide highly viable leads for the development anti-tau-phosphorylation agents with a view to eventually ameliorating Alzheimer's disease.
A new class of compounds, namely highly substituted diaminocyclopentane-l-lysine adducts, have been discovered as potent inhibitors O-GlcNAcase, an enzyme crucial for protein de-O-glycosylation. These exhibit exceptional selectivity and reversibility are the first example human O-GlcNAcase that structurally related to transition state rate-limiting step with "aglycon" still in bond-length proximity. The ease their preparation, remarkable biological activities, stability, non-toxicity make...
In many γ-proteobacteria, the RpoS/σS sigma factor associates with core RNAP (RNA polymerase) to modify global gene transcription in stationary phase and under stress conditions. The small regulatory protein Crl stimulates association of σS Escherichia coli Salmonella enterica serovar Typhimurium, through direct specific interaction σS. structural determinants involved binding are unknown. present paper we report X-ray crystal structure Proteus mirabilis (CrlPM) a model for Typhimurium...
Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series new cyclopentanoid β-galactosidase were prepared and their inhibitory chaperoning activities determined compared with those lipophilic analogs the potent β-d-galactosidase inhibitor 4-epi-isofagomine. Structure-activity relationships investigated by X-ray crystallography well alterations in cyclopentane moiety such deoxygenation replacement fluorine...