A5069572460- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Neurological diseases and metabolism
- Origins and Evolution of Life
- Metabolism and Genetic Disorders
- Biochemical and Structural Characterization
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Invertebrate Immune Response Mechanisms
- Biomedical Text Mining and Ontologies
- Bioinformatics and Genomic Networks
- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
- Fungal and yeast genetics research
- Microbial Metabolic Engineering and Bioproduction
- Mitochondrial Function and Pathology
- Genomics and Phylogenetic Studies
- Genetics, Bioinformatics, and Biomedical Research
- Protist diversity and phylogeny
- Aquaculture disease management and microbiota
- Research on Leishmaniasis Studies
- Viral Infections and Vectors
Charles University
2012-2024
University of Cambridge
2024
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2024
European Bioinformatics Institute
2024
Georgia State University
2024
Czech Academy of Sciences
2024
Výzkumná Stanice Vinohradnická
2021
Linnaeus University
2005-2007
Uppsala University
2003-2007
PrankWeb is an online resource providing interface to P2Rank, a state-of-the-art method for ligand binding site prediction. P2Rank template-free machine learning based on the prediction of local chemical neighborhood ligandability centered points placed solvent-accessible protein surface. Points with high score are then clustered form resulting sites. In addition, provides web enabling users easily carry out and visually inspect predicted sites via integrated sequence-structure view....
Abstract The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository manually curated annotations intrinsically disordered proteins and regions from literature. We report here recent updates DisProt version 9, including a restyled web interface, refactored Ontology (IDPO), improvements in curation process significant content growth around 30%. Higher quality consistency provided by newly implemented reviewing training curators. increased...
Knowledge of protein-ligand binding sites (LBSs) enables research ranging from protein function annotation to structure-based drug design. To this end, we have previously developed a stand-alone tool, P2Rank, and the web server PrankWeb (https://prankweb.cz/) for fast accurate LBS prediction. Here, present significant enhancements PrankWeb. First, new, more evolutionary conservation estimation pipeline based on UniRef50 sequence database HMMER3 package is introduced. Second, now allows users...
Trichomonas vaginalis is a parasitic protist of the Excavata group. It contains an anaerobic form mitochondria called hydrogenosomes, which produce hydrogen and ATP; majority mitochondrial pathways organellar genome were lost during mitochondrion-to-hydrogenosome transition. Consequently, all hydrogenosomal proteins are encoded in nucleus imported into organelles. However, little known about membrane machineries required for biogenesis organelle metabolite exchange. Using combination mass...
Abstract When a new protein structure has been determined, comparison with the database of known structures enables classification its fold as or belonging to class proteins. This in turn may provide clues about function protein. A large number programs have developed, but they never subjected comprehensive and critical comparative analysis. Here we describe an evaluation 11 publicly available, Web‐based servers for automatic comparison. Both their functionality (e.g., user interface,...
Involvement of conservative molecular modules and cellular mechanisms in the widely diversified processes eukaryotic cell morphogenesis leads to intriguing question: how do similar proteins contribute dissimilar morphogenetic outputs. Formins (FH2 proteins) play a central part control actin organization dynamics, providing good example evolutionarily versatile use conserved protein domain context variety lineage-specific structural signalling interactions. In order identify possible...
Melanization is an important immune component of the innate system invertebrates and vital for defense as well wound healing. In most melanin synthesis achieved by prophenoloxidase-activating system, a proteolytic cascade similar to vertebrate complement. Even though formation necessary host in crustaceans insects, process needs be tightly regulated because hazard animal unwanted production quinone intermediates melanization places where it not suitable. present study we have identified new...
Hematopoiesis is the process by which hemocytes mature and subsequently enter circulation. Vertebrate prokineticins (PKs) are known to take part in this process, as invertebrate prokineticin domain proteins, astakines. In Pacifastacus leniusculus, astakine 1 essential for release of new into open circulatory system these animals. addition 1, we have now cloned a homologue with an insert 13 amino acids, named 2. Both crustacean astakines lack N-terminal AVIT motif, present vertebrate PKs,...
Abstract N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of use-dependent voltage-independent inhibitory effect neurosteroids on NMDAR responses. The site action located at extracellular vestibule receptor’s ion channel pore accessible after receptor...
Recent findings in protein evolution and peptide prebiotic plausibility have been setting the stage for reconsidering role of peptides early stages life’s origin. Ancient families found to share common themes proteins reduced composition prebiotically plausible amino acids reported capable structure formation key functions, such as binding RNA. While this may suggest relevance life, their functional repertoire when composed a limited number residues (missing some most sophisticated groups...
Mitochondrial processing peptidases are heterodimeric enzymes (alpha/betaMPP) that play an essential role in mitochondrial biogenesis by recognizing and cleaving the targeting presequences of nuclear-encoded proteins. The two subunits paralogues probably evolved duplication a gene for monomeric metallopeptidase from endosymbiotic ancestor mitochondria. Here, we characterize MPP-like proteins important human parasites contain highly reduced versions mitochondria, mitosomes Giardia...
Mitochondria originated from proteobacterial endosymbionts, and their transition to organelles was tightly linked establishment of the protein import pathways. The initial most proteins is mediated by translocase outer membrane (TOM). Although TOM common all forms mitochondria, an unexpected diversity subunits between eukaryotic lineages has been predicted. However, experimental knowledge limited a few organisms, so far, it remains unsettled whether triplet-pore or twin-pore structure...
Human glutathione transferase A1-1 is a well studied enzyme, but despite wealth of structural and biochemical data number aspects its catalytic function are still poorly understood. Here, five new crystal structures this enzyme described that provide several insights. Firstly, the structure complex wild-type human with was determined for first time at 2.0 Å resolution. This reveals binds in G site very similar fashion as portion substrate analogues other also binding alone sufficient to...
Crk-associated substrate (CAS) is a major tyrosine-phosphorylated protein in cells transformed by v-crk and v-src oncogenes plays an important role invasiveness of Src-transformed cells. A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket CAS SH3 domain, was identified found to be enriched invasive human carcinoma To study biological significance Y12 phosphorylation, phosphomimicking Y12E nonphosphorylatable Y12F mutants were studied. The mutation...
Background SH3 domains are eukaryotic protein that participate in a plethora of cellular processes including signal transduction, proliferation, and movement. Several studies indicate tyrosine phosphorylation could play significant role the regulation domains. Results To explore incidence within we queried PhosphoSite Plus database sites. Over 100 phosphorylations occurring on 20 different domain positions were identified. The corresponding to c–Src Tyr-90 was by far most frequently...
Saccharomyces cerevisiae uses several mechanisms for arsenic detoxification including the arsenate reductase Acr2p and arsenite efflux protein Acr3p. ACR2 ACR3 are transcribed in opposite directions from same promoter expression of these genes is regulated by AP-1 (activator 1)-like transcription factor Yap8p. Yap8p has been shown to permanently associate with this stimulate ACR2/ACR3 response arsenic. In present study we characterized DNA sequence that targeted We show binds a...
A single protein structure is rarely sufficient to capture the variability of a protein. Both bound and unbound (holo apo) forms are essential for understanding its geometry making meaningful comparisons. Nevertheless, docking or drug design studies often still consider only structures in their holo form, which most part rigid. With recent explosion field structural biology, large, curated datasets urgently needed. Here, we use previously developed application (AHoJ) perform comprehensive...
A single protein structure is rarely sufficient to capture the conformational variability of a protein. Both bound and unbound (holo apo) forms are essential for understanding its geometry making meaningful comparisons. Nevertheless, docking or drug design studies often still consider only structures in their holo form, which most part rigid. With recent explosion field structural biology, large, curated datasets urgently needed. Here, we use previously developed application (AHoJ) perform...
Abstract CAS is a docking protein downstream of the proto-oncogene Src with role in invasion and metastasis cancer cells. The SH3 domain indispensable for CAS-mediated signaling, but structural aspects ligand binding regulation are not well understood. Here, we identified consensus motif structurally characterized complex ligand. We revealed requirement an uncommon centrally localized lysine residue at position +2 ligands two rather dissimilar optional anchoring residues, leucine arginine,...
The fact that protein structures are dynamic by nature and structure models determined X-ray crystallography, electron microscopy (EM) nuclear magnetic resonance (NMR) spectroscopy have limited accuracy limits the precision with which derived properties can be reported. Here, issue of calculated solvent-accessible surface areas (ASAs) is addressed. A number different sizes were selected effect random shifts applied to atomic coordinates on ASA values was investigated. Standard deviations...
Yellow-related proteins (YRPs) present in sand fly saliva act as affinity binders of bioamines, and help the to complete a bloodmeal by scavenging physiological signals damaged cells. They are also main antigens their recombinant form is used marker host exposure flies. Moreover, several salivary plasmids coding these induce strong immune response hosts bitten flies being design protecting vaccines against Leishmania parasites. In this study, thirty two 3D models different yellow-related...