A5031394756- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Enzyme Production and Characterization
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Lysosomal Storage Disorders Research
- Neonatal Health and Biochemistry
- Porphyrin Metabolism and Disorders
- Biofuel production and bioconversion
- Heme Oxygenase-1 and Carbon Monoxide
- Machine Learning in Materials Science
- Enzyme Catalysis and Immobilization
- Radiomics and Machine Learning in Medical Imaging
- Computational Drug Discovery Methods
- Metabolism and Genetic Disorders
- Microbial Natural Products and Biosynthesis
- Trypanosoma species research and implications
- Cellular transport and secretion
- Microbial Community Ecology and Physiology
Leiden University
2016-2024
Institute of Chemistry
2020-2021
CIC bioGUNE
2014-2018
Every organism across the tree of life compacts and organizes its genome with architectural chromatin proteins. While eukaryotes archaea express histone proteins, organization bacterial chromosomes is dependent on nucleoid-associated In Escherichia coli other proteobacteria, histone-like nucleoid structuring protein (H-NS) acts as a global organizer gene regulator. Functional analogues H-NS have been found in species: MvaT Pseudomonas species, Lsr2 actinomycetes Rok Bacillus species. These...
The off-patent marketed antifungal ciclopirox improves symptoms in a mouse model of congenital erythropoietic porphyria.
Abstract H-NS proteins act as osmotic sensors translating changes in osmolarity into altered DNA binding properties, thus, regulating enterobacterial genome organization and genes transcription. The molecular mechanism underlying the switching process its conservation among family members remains elusive. Here, we focus on protein MvaT from Pseudomonas aeruginosa demonstrate experimentally that protomer exists two different conformations, corresponding to functional states. In half-opened...
Glucocerebrosidase (GBA) is a lysosomal β-glucosidase that degrades glucosylceramide. Its deficiency results in Gaucher disease (GD). We examined the effects of active site occupancy GBA on its structural stability. For this, we made use cyclophellitol-derived activity-based probes (ABPs) bind irreversibly to catalytic nucleophile (E340), and for comparison, used potent reversible inhibitor isofagomine. demonstrate cyclophellitol ABPs improve stability vitro, as revealed by thermodynamic...
Congenital erythropoietic porphyria (CEP) results from a deficiency in uroporphyrinogen III synthase enzyme (UROIIIS) activity that ultimately stems deleterious mutations the uroS gene. C73 is hotspot for these and C73R substitution, which drastically reduces stability, found almost one-third of all reported CEP cases. Here, we have studied structural basis, by this lead to UROIIIS destabilization. First, strong interdependency observed between volume side chain at position 73 folded...
Glycoside hydrolases (GHs) are attractive tools for multiple biotechnological applications. In conjunction with their hydrolytic function, GHs can perform transglycosylation under specific conditions. nature, oligosaccharide synthesis is performed by glycosyltransferases (GTs); however, the industrial use of GTs limited instability in solution. A key difference between and flexibility binding site architecture. We have used xylanase from Bacillus circulans (BCX) to study interplay...
Bacillus circulans xylanase (BcX) from the glycoside hydrolase family 11 degrades xylan through a retaining, double-displacement mechanism. The enzyme is thought to hydrolyze glycosidic bonds in processive manner and has large, active site cleft, with six subsites allowing binding of xylose units. Such an architecture suggests that oligomeric substrates can bind multiple ways. In crystal structure catalytically inactive variant BcX E78Q, substrate xylotriose observed site, as well bound...
H-NS family proteins, bacterial xenogeneic silencers, play central roles in genome organization and the regulation of foreign genes. It is thought that gene repression directly dependent on DNA binding modes proteins. These proteins form lateral protofilaments along DNA. Under specific environmental conditions they switch to bridging two duplexes. This switching a direct effect electrostatic interactions between oppositely charged N-terminal domains The Pseudomonas lytic phage LUZ24 encodes...
Glycosyl hydrolases (GHs) are carbohydrate-active enzymes that hydrolyze a specific β-glycosidic bond in glycoconjugate substrates; β-glucosidases degrade glucosylceramide, ubiquitous glycosphingolipid. GHs grouped into structurally similar families themselves can be clans. GH1, GH5, and GH30 glycosidases belong to clan A with catalytic (β/α)8 TIM barrel domain, whereas GH116 belongs O (α/α)6 domain. In humans, GH abnormalities underlie metabolic diseases. The lysosomal enzyme...
Small compound active site interactors receive considerable attention for their ability to positively influence the fold of glycosidases. Endoglycoceramidase II (EGCII) from Rhodococcus sp. is an endo-β-glucosidase releasing complete glycan ceramide in glycosphingolipids. Cleavage β-glycosidic linkage between glucose and also catalyzed by glucocerebrosidase (GBA), exo-β-glucosidase deficient Gaucher disease. We demonstrate that established β-glucoside-configured cyclophellitol-type...
The single-domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which one most abundant renewable biomaterials nature. We demonstrate that BCX solution undergoes minimal structural changes during turnover. NMR spectroscopy results show rigid protein matrix provides a frame for fast substrate binding multiple conformations, accompanied by slow conversion, attributed to an enzyme-induced distortion. A model proposed enzyme takes advantage...
Abstract H-NS proteins act as osmotic sensors translating changes in osmolarity into altered DNA binding properties, thus, regulating enterobacterial genome organization and genes transcription. The molecular mechanism underlying the switching process its conservation among family members remains elusive. Here, we focus on protein MvaT from P. aeruginosa demonstrate experimentally that protomer exists two different conformations, corresponding to functional states. In half-opened state...
Abstract Glycoside hydrolases (GH) are attractive tools for multiple biotechnological applications. In conjunction with their hydrolytic function, GH can perform transglycosylation reaction under specific conditions. nature, oligosaccharides synthesis is performed by glycosyltransferase (GT). However, the industrial utilization of GT limited instability in solution. A key difference between and flexibility binding sites architecture. this report, we used xylanase from Bacillus circulans...
Abstract The single‐domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which one most abundant renewable biomaterials nature. We demonstrate that BCX solution undergoes minimal structural changes during turnover. NMR spectroscopy results show rigid protein matrix provides a frame for fast substrate binding multiple conformations, accompanied by slow conversion, attributed to an enzyme‐induced distortion. A model proposed enzyme takes...
Abstract Many enzymes are dynamic entities, sampling conformational states that relevant for catalytic activity. Crystal structures of intermediates suggest, however, not all require structural changes The single-domain enzyme xylanase from Bacillus circulans (BCX) is involved in the degradation hemicellulose. We demonstrate BCX solution undergoes minimal during catalysis. NMR spectroscopy results show rigid protein matrix provides a frame fast substrate binding multiple conformations,...
Abstract H-NS family proteins, bacterial xenogeneic silencers, play central roles in genome organization and the regulation of foreign genes. It is thought that gene repression directly dependent on DNA binding modes proteins. These proteins form lateral protofilaments along DNA. Under specific environmental conditions they switch to bridging two duplexes. This switching a direct effect electrostatic interactions between oppositely charged N-terminal domains The Pseudomonas lytic phage LUZ24...