A5058332995- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Various Chemistry Research Topics
- Crystal structures of chemical compounds
- Signaling Pathways in Disease
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Synthesis of Organic Compounds
- Plant Virus Research Studies
- Chemistry and Chemical Engineering
- S100 Proteins and Annexins
- Microbial Metabolic Engineering and Bioproduction
- Fluorine in Organic Chemistry
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Photochromic and Fluorescence Chemistry
- Protease and Inhibitor Mechanisms
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Fungal and yeast genetics research
- Escherichia coli research studies
Technion – Israel Institute of Technology
2004-2024
Weizmann Institute of Science
2015
W. M. Keck Foundation
2012
Cold Spring Harbor Laboratory
2012
Howard Hughes Medical Institute
2012
Universität Innsbruck
2007
Laboratoire de Chimie de Coordination
2004
Centre National de la Recherche Scientifique
2004
Alzheimer's disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination essential for clearance cells, making altered ubiquitin signaling crucial AD development. A defective variant, B + 1 (UBB+1), created a non-hereditary RNA frameshift mutation, found all patient brains post-mortem. We now detect UBB+1 human during early stages. Our study employs 3D neural culture platform derived from progenitors, demonstrating that alone induces extracellular amyloid-β (Aβ)...
A wealth of genetic information and some biochemical analysis have made the GAL regulon yeast Saccharomyces cerevisiae a classic model system for studying transcriptional activation in eukaryotes. Galactose induces this switch, which is regulated by three proteins: activator Gal4p, bound to DNA; repressor Gal80p; transducer Gal3p. We showed previously that NADP appears act as trigger kick off activator. Sustained involves complex Gal3p Gal80p mediated galactose ATP. solved crystal structure...
Three cocrystals of the light-stable compound 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol (I) with light-sensitive molecules 1,2-dimethyl-2(1H)-pyridinone (a), 6-methyl-2(1H)-pyridinone (b) and 2-methyl-2(1H)-pyridinone (c) were exposed to UV light. It was found that undergo molecular flip perpendicular plane (rotation ∼180°). In first two cocrystals, are disordered, which means space provided for them is larger than needed ordered molecules. Therefore, rotation can take place. Moreover, in...
The ubiquitin (Ub)-proteasome system is the primary mechanism for maintaining protein homeostasis in eukaryotes, yet underlying signaling events and specificities of its components are poorly understood. Proteins destined degradation tagged with covalently linked polymeric Ub chains subsequently delivered to proteasome, often assistance shuttle proteins that contain Ub-like domains. This pathway riddled apparent redundancy-in form numerous polyubiquitin various lengths distinct...
Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix. MMP-9 has been implicated in several diseases including neurodegeneration, arthritis, cardiovascular diseases, fibrosis and types of cancer, resulting a high demand for inhibitors therapeutic purposes. For such drug design efforts, large amounts are required. Yet, catalytic domain (MMP-9Cat) intrinsically unstable enzyme tends to auto-cleave within minutes, making it difficult use experiments other...
Derived from the yeast whole-genome duplication, Saccharomyces cerevisiae GAL1 and GAL3 encode catabolic enzyme galactokinase (Gal1) its transcriptional coinducer (Gal3), whereas ancestral, preduplicated gene performed both functions. Previous studies indicated that divergence was primarily driven by changes in upstream promoter elements, GAL3's coding region are assumed to be result of drift. We show replacement open-reading-frame with GAL1's results an extended lag phase upon switching...
Abstract Photochemical dimerization reactions of 1,3‐diphenyl‐1‐propen‐3‐one (chalcone), 9‐acetylanthracene, and 9‐(methoxycarbonyl)anthracene as guest molecules in inclusion compounds with 1,1,6,6‐tetraphenyl‐2,4‐hexadiyne‐1,6‐diol were studied. The irradiation a single crystal containing chalcone was carried out step resulted the photodimer full occupancy. In case X‐ray diffraction data collected after for different periods time. Only one two crystallographically independent pairs...
Proteasomes are multi-subunit, multi-catalytic protein complexes present in eukaryotic cells that degrade misfolded, damaged, or unstructured proteins. In this study, we used an activity-guided proteomic methodology based on a fluorogenic peptide substrate to characterize the composition of proteasome WT yeast and changes these undergo upon deletion Pre9 (Δα3) Sem1 (ΔSem1).A comparison whole-cell analysis profiling indicates amounts proteasomal proteins interacting assembled active...
Six inclusion compounds containing a photoreactive guest molecule, 4-oxo(phenylacetyl)morpholine or 1-(phenylglyoxylyl)piperidine, with different host molecules have been crystallized. The underwent photochemical reaction upon irradiation. Examining their structures suggests that γ-hydrogen abstraction by an oxygen, the first step in cyclization of α-oxoamides, should be possible all cases. In four cases crystallinity was maintained during and at end conversion process i.e. single-crystal to...
Abstract Two inclusion compounds that contain a light‐stable host molecule and light‐sensitive guest have been crystallized, is, 4,5‐bis(hydroxydiphenylmethyl)‐2,2‐dimethyl‐1,3‐dioxolane as the with tropolone methyl ether 2,3‐bis(hydroxydiphenylmethyl)‐1,4‐dioxaspiro[4.5]decane 4‐(oxophenylacetyl)morpholine molecule. The two undergo photochemical ring‐closure reactions. However, while first reacts by heterogeneous process, second undergoes homogeneous photoreaction. X‐ray crystal structure...
Photodimerizations of pyridone or methyl which serve as guest molecules in crystalline inclusion compounds are associated with a decrease the volume molecules; at end this single crystal to transformation channels formed through water diffuse.
Abstract 1‐Methyl‐ and 1‐ethyl‐5,6‐diphenylpyrazin‐2‐one crystallize in two modifications, one of which is light‐stable the other light‐sensitive. The light‐sensitive modification known to undergo photodimerization solid state. This polymorph crystallizes monoclinic space group P 2 1 with crystallographically independent molecules asymmetric unit. are packed stacks running parallel unique b axis. arranged alternately along stack. In principle, there different pairs within a stack that can...
The crystal structures of two cocrystals composed 4,4′-(fluorene-9,9-diyl)diphenol (C25H18O2) and 6-methyl-2H-pyridone (C6H7NO) are reported, namely 4,4′-(fluorene-9,9-diyl)diphenol–6-methyl-2H-pyridone (1/2), C25H18O2·2C6H7NO, (I), 4,4′-(fluorene-9,9-diyl)diphenol–6-methyl-2H-pyridone–water (1/3/3), C25H18O2·3C6H7NO·3H2O, (II). In both cocrystals, the mutual orientation between molecules in principle enables photodimerization, yet cases no photodimerization occurs. cocrystal (I) this is...
Cyclooxygenase-2 (COX-2) catalyzes the oxidation of arachidonic acid (AA) into a single product that is source all prostaglandins (PGs), ligands multiple pro-inflammatory pathways. AA catalysis results in suicide inactivation, rendering enzyme catalytically inactive. Here, we report catalytic activity also leads to controlled cleavage COX-2, an event differentially regulated by fatty acids, and blocked COX inhibitors. We find COX-2 fragments human colon tumors. Using mass spectrometry,...
Summary The N-termini of proteins contain information about their biochemical properties and functions. These can be processed by proteases undergo other co- or post-translational modifications. We have developed LATE (LysN Amino Terminal Enrichment), a method that uses selective chemical derivatization α-amines to isolate the N-terminal peptides, in order improve N-terminome identification conjunction with enrichment strategies. applied alongside another N-terminomic study caspase-3...
Abstract Virophages are small dsDNA viruses dependent on a nucleocytoplasmic large-DNA virus infection of cellular host for replication. Putative virophages infecting algal hosts classified together with polinton-like viruses, transposable elements widely found in genomes, yet the lack isolated strains raises questions about their existence as independent entities. In this work we and characterized virophage (PgVV-14T) co-infecting Phaeocystis globosa virus-14T (PgV-14T). PgVV-14T decreases...
The crystal structures of three 1:2 inclusion compounds that consist host molecule 2,5-diphenylhydroquinone (C(18)H(14)O(2)) and the guest molecules 2-pyridone (C(5)H(5)NO), 1,3-diphenyl-2-propen-1-one (chalcone, C(15)H(12)O) 1-(4-methoxyphenyl)-3-phenyl-2-propen-1-one (4'-methoxychalcone, C(16)H(14)O(2)) were determined in order to study ability undergo photoreaction. All crystals found be photoresistant. crystallize triclinic space group P1. In each case, host/guest ratio is 1:2, with...
Abstract Proteasomes are multi-subunit, multi-catalytic protein complexes present in eukaryotic cells that degrade misfolded, damaged, or unstructured proteins. In this study, we used an activity-guided proteomic methodology based on a fluorogenic peptide substrate to characterize the composition of proteasome WT yeast, and changes these undergo upon deletion Pre9 (Δα3) Sem1 (ΔSem1). A comparison whole-cell analysis profiling indicates amounts proteasomal proteins interacting assembled...
Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix and has been implicated as a major driver in cancer metastasis. Hence, there high demand for MMP-9 inhibitors therapeutic purposes. For such drug design efforts, large amounts of are required. Yet, catalytic domain (MMP-9
MSmost recent studies and unpublished data.In particular, I will present our current model for transcription initiation at a gene promoter [1], the most insights into elongation, in particular how RNA polymerase II can arrest then be reactivated [2], only universally conserved factor, Spt5 (or NusG bacteria), prevents premature termination by enclosing DNA rendering processive [3].