A5053742158- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Sphingolipid Metabolism and Signaling
- Cancer Treatment and Pharmacology
- Endoplasmic Reticulum Stress and Disease
- Enzyme function and inhibition
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Protein Structure and Dynamics
- Cannabis and Cannabinoid Research
- Natural product bioactivities and synthesis
- Enzyme Structure and Function
- Corporate Governance and Law
- Crystallography and molecular interactions
- European and International Contract Law
- Calcium signaling and nucleotide metabolism
- Axial and Atropisomeric Chirality Synthesis
- Plant-derived Lignans Synthesis and Bioactivity
- Heat shock proteins research
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Metal-Catalyzed Oxygenation Mechanisms
- Ion Transport and Channel Regulation
Carl von Ossietzky Universität Oldenburg
2022-2024
European Molecular Biology Laboratory
2022-2024
European Molecular Biology Laboratory
2022-2023
The Netherlands Cancer Institute
2010-2016
University of Michigan
2010
Utrecht University
2010
The molecular chaperone Hsp90 is a protein folding machine that conserved from bacteria to man. Human, cytosolic dedicated of chiefly signal transduction components. chaperoning mechanism controlled by ATP and various cochaperones, but poorly understood controversial. Here, we characterized the Apo states 170-kDa human full-length NMR spectroscopy in solution, elucidated inhibition its ATPase cochaperone p23. We assigned isoleucine side chains via specific isotope labeling their δ-methyl...
Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression, rendering ATX an attractive drug target. We recently described boronic acid-based inhibitor of ATX, named HA155 (1). Here, we report design new inhibitors based on crystal structure complex with 1. Furthermore, describe syntheses...
Abstract Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus tumour progression. ATX has a tripartite active site, combining hydrophilic groove, hydrophobic lipid-binding pocket tunnel of unclear function. We present crystal structures rat bound to 7α-hydroxycholesterol bile salt tauroursodeoxycholate (TUDCA), showing how...
Introduction The potassium chloride cotransporter 4 (KCC4) is expressed in various tissues and plays an important role distal renal acidification hearing development. Although KCCs transport K + Cl − a 1:1 stoichiometry, two coordination sites were indicated via cryo-electron microscopy (CryoEM). Methods In comprehensive analysis, we analyzed here the consequences of point mutation residues coordinating potassium, first (Cl 1 ) second 2 site KCC4 using Tl based flux measurements. Results...
Autotaxin (ATX) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), playing key role in diverse physiological and pathological processes. ATX exists distinct splice variants, but isoform-specific functions remain elusive. Here we characterize ATXα isoform, which differs from canonical form (ATXβ) having 52-residue polybasic insertion of unknown function catalytic domain. We find susceptible to cleavage by extracellular furin-like endoproteases,...
Hsp33, a molecular chaperone specifically activated by oxidative stress conditions that lead to protein unfolding, protects cells against aggregation. Stress sensing in Hsp33 occurs via its C-terminal redox switch domain, which consists of zinc center responds the presence oxidants and an adjacent metastable linker region, unfolding conditions. Here we show single mutations N terminus are sufficient either partially (Hsp33-M172S) or completely (Hsp33-Y12E) abolish this post-translational...
Autotaxin is primarily known for the formation of lysophosphatidic acid (LPA) from lysophosphatidylcholine. LPA an important signaling phospholipid that can bind to six G protein–coupled receptors (LPA 1–6 ). The ATX-LPA axis a critical component in many physiological and pathophysiological conditions. Here, we describe potent inhibition Δ 9 - trans -tetrahydrocannabinol (THC), main psychoactive compound medicinal cannabis related cannabinoids, on catalysis two isoforms ATX with nanomolar...
Autotaxin (ATX or ENPP2) is a secreted glycosylated mammalian enzyme that exhibits lysophospholipase D activity, hydrolyzing lysophosphatidylcholine to the signalling lipid lysophosphatidic acid. ATX an ∼100 kDa multi-domain protein encompassing two N-terminal somatomedin B-like domains, central catalytic phosphodiesterase domain and C-terminal nuclease-like domain. Protocols for efficient expression of from stably transfected HEK293 cells in amounts sufficient crystallographic studies are...
Abstract One goal of the CASP community wide experiment on critical assessment techniques for protein structure prediction is to identify current state art in and modeling. A fundamental principle blind a set relevant targets, that is, participating computational methods are tested common experimental target proteins, which structures not known at time Therefore, would have been possible without broad support structural biology community. In this article, several groups discuss proteins they...
Over the past few decades, many current uses for cannabinoids have been described, ranging from controlling epilepsy to neuropathic pain and anxiety treatment. Medicines containing approved by both FDA EMA control of specific diseases which there are alternatives. However, molecular-level mechanism action is still poorly understood. Recently, shown interact with autotaxin (ATX), a secreted lysophospholipase D enzyme responsible catalyzing lysophosphatidylcholine (LPC) lysophosphatidic acid...
Rat autotaxin has been cloned, expressed, purified to homogeneity and crystallized via hanging-drop vapour diffusion using PEG 3350 as precipitant ammonium iodide sodium thiocyanate salts. The crystals diffracted a maximum resolution of 2.05 Å belonged space group P 1, with unit-cell parameters = 53.8, b 63.3, c 70.5 Å, α 98.8, β 106.2, γ 99.8°. Preliminary X-ray diffraction analysis indicated the presence one molecule per asymmetric unit, solvent content 47%.
Autotaxin (ATX) is an enzyme primarily known for the production of lysophosphatidic acid. Being involved in development major human diseases, such as cancer and neurodegenerative has been featured multiple studies a pharmacological target. We previously found that cannabinoid tetrahydrocannabinol (THC) could bind act excellent inhibitor ATX. This study aims to use scaffold starting point find cannabinoid-unrelated ATX inhibitors, following funnel down approach which large chemical libraries...
Abstract Retinal degeneration protein 3 (RD3) plays a crucial role in controlling guanylate cyclase activity photoreceptor rod and cone cells, mediates trafficking processes within cells. Loss of RD3 function correlates with severe forms retinal dystrophy the development aggressive neuroblastoma cancer. In present study, we analysed expression by applying data-mining approach using public databases. addition, performed an transcript analysis on specimens glioma tissues from patients. We...
Autotaxin (ATX) is an enzyme primarily known for the production of lysophosphatidic acid. Being involved in development major human diseases, such as cancer and neurodegenerative has been featured multiple studies a pharmacological target. We previously found that cannabinoid tetrahydrocannabinol (THC) could bind act excellent inhibitor ATX. This study aims to use scaffold starting point find cannabinoid-unrelated ATX inhibitors, following funnel down approach which large chemical libraries...
The functional importance of neuronal differentiation the transmembrane proteins' plasticity-related genes 3 (PRG3) and 5 (PRG5) has been shown. Although their sequence is closely related, they promote different morphological changes in neurons. PRG3 was shown to neuritogenesis primary neurons; PRG5 contributes spine induction immature neurons regulation density morphology mature Both exhibit intracellularly located C-termini less than 50 amino acids. Varying suggested that these domains...