A5049132537- Parasites and Host Interactions
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Parasite Biology and Host Interactions
- Vector-borne infectious diseases
- Trace Elements in Health
- Research on Leishmaniasis Studies
- Helminth infection and control
- Insect Resistance and Genetics
- Trypanosoma species research and implications
- Bone Metabolism and Diseases
- Galectins and Cancer Biology
- Toxin Mechanisms and Immunotoxins
- Enzyme Production and Characterization
- Biochemical and Structural Characterization
- Invertebrate Immune Response Mechanisms
- Malaria Research and Control
- Coccidia and coccidiosis research
- Phytase and its Applications
- Advanced Biosensing Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Antimicrobial Peptides and Activities
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2014-2024
Czech Academy of Sciences
2002-2021
Max Planck Institute for Chemical Ecology
2001-2005
Charles University
2005
Scienion (Germany)
2003
Max Planck Society
1999-2001
GlaxoSmithKline (United Kingdom)
2001
Background The possible emergence of resistance to the only available drug for schistosomiasis spurs discovery that has been recently incentivized by availability improved transcriptome and genome sequence information. Transient RNAi emerged as a straightforward important technique interrogate information through decreased or loss gene function identify potential targets. To date, studies in schistosome stages infecting humans have focused on single (or up 3) genes interest. Therefore,...
Abstract Background Ticks are vectors of a wide variety pathogens causing severe diseases in humans and domestic animals. Intestinal digestion the host blood is an essential process tick physiology also limiting factor for pathogen transmission since gut represents primary site infection proliferation. Using model Ixodes ricinus , European Lyme disease vector, we have previously demonstrated by genetic biochemical analyses that degraded network acidic peptidases aspartic cysteine classes....
There is burgeoning interest in protein microarrays, but a source of thousands nonredundant, purified proteins was not previously available. Here we show glass chip containing 2413 nonredundant human fusion on polymer surface, where densities up to 1600 proteins/cm2 microscope slide can be realized. In addition, the coating enables screening interactions under nondenaturing conditions. Such screenings require only 200-μl sample volumes, illustrating their potential for high-throughput...
Ticks are vectors for a variety of viral, bacterial and parasitic diseases in human domestic animals. To survive reproduce ticks feed on host blood, yet our understanding the intestinal proteolytic machinery used to derive absorbable nutrients from blood meal is poor. Intestinal digestive processes limiting factors pathogen transmission since tick gut presents primary site infection. Moreover, enzymes may find practical application as anti-tick vaccine targets.Using hard tick, Ixodes...
Schistosomiasis caused by a parasitic blood fluke of the genus Schistosoma afflicts over 200 million people worldwide. mansoni cathepsin B1 (SmCB1) is gut-associated peptidase that digests host proteins as source nutrients. It under investigation drug target. To further this goal, we report three crystal structures SmCB1 complexed with peptidomimetic inhibitors follows: epoxide CA074 at 1.3 Å resolution and vinyl sulfones K11017 K11777 1.8 2.5 resolutions, respectively. Interactions subsites...
The saliva of blood-feeding parasites is a rich source peptidase inhibitors that help to overcome the host's defence during host–parasite interactions. Using proteomic analysis, cystatin OmC2 was demonstrated in soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and spirochaete Borrelia duttoni. A structural, biochemical biological characterization this inhibitor undertaken present study. Recombinant screened against panel physiologically...
Two genes coding for cysteine peptidase inhibitors of the cystatin family (Om-cystatin 1 and 2) were isolated from a gut-specific cDNA library soft tick Ornithodoros moubata. Both cystatins clearly down-regulated after blood meal. Om-cystatin is mainly expressed in gut, while 2 mRNA was also found other tissues. Authentic significantly more abundant than gut contents fasting ticks associated with hemosome-derived residual bodies accumulated lumen. by type secretory cells salivary glands...
Abstract A coumarin‐tetrahydroquinoline hydride 8 was synthesized as a chemical tool for fluorescent labeling. The rigidified tricyclic coumarin structure chosen its suitable fluorescence properties. connection of with vinyl sulfone building block accomplished by convergent synthesis thereby leading to the coumarin‐based, tripeptidomimetic activity‐based probe 10 , containing Gly‐Phe‐Gly motif. Probe evaluated inactivator therapeutically relevant human cysteine cathepsins S, L, K, and B: it...
The quantum mechanics (QM)-based scoring function that we previously developed for the description of noncovalent binding in protein–ligand complexes has been modified and extended to treat covalent inhibitory ligands. enhancements are (i) bond breakage formation using hybrid QM/semiempirical QM (QM/SQM) restrained optimizations (ii) addition new ΔGcov′ term score, describing "free" energy difference between complexes. This enhanced QM-based is applied a series 20 vinyl sulfone-based...
Background Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is need to identify new targets chemotherapeutic interventions. Our research focused on mansoni prolyl oligopeptidase (SmPOP) from serine peptidase family S9, has not been investigated in detail trematodes. Methodology/Principal Findings We demonstrate SmPOP expressed adult worms schistosomula an enzymatically active form. By...
Schistosomiasis, caused by a parasitic blood fluke of the genus Schistosoma, is global health problem for which new chemotherapeutic options are needed. We explored scaffold gallinamide A, natural peptidic metabolite marine cyanobacteria that has previously been shown to inhibit cathepsin L-type proteases. screened library 19 synthetic A analogs and identified nanomolar inhibitors B-type protease SmCB1, drug target treatment schistosomiasis mansoni. Against cultured S. mansoni schistosomula...
The digestive tract of lepidopteran insects is extremely alkaline. In the present work, molecular adaptation amylolytic enzymes to this environment was investigated in flour moth Ephestia kuehniella, an important stored-product pest. Three alpha-amylases [Ephestia kuehniella alpha-amylase isoenzymes 1-3 (EkAmy1-3)] with alkaline pH optimum were purified from larvae and biochemically characterized. These differ significantly their sensitivity inhibitors plant origin that are directed against...
Background Blood flukes (Schistosoma spp.) are parasites that can survive for years or decades in the vasculature of permissive mammalian hosts, including humans. Proteolytic enzymes (proteases) crucial successful parasitism, aspects invasion, maturation and reproduction. Most attention has focused on 'cercarial elastase' serine proteases facilitate skin invasion by infective schistosome larvae, cysteine aspartic worms use to digest blood meal. Apart from cercarial elastases, information...
Background Serine proteases are important virulence factors for many pathogens. Recently, we discovered a group of trypsin-like serine with domain organization unique to flatworm parasites and containing thrombospondin type 1 repeat (TSR-1). These recognized as antigens during host infection may prove useful anthelminthic vaccines, however their molecular characteristics under-studied. Here, characterize the structural proteolytic attributes protease 2 (SmSP2) from Schistosoma mansoni, one...