A5084896156- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Cell Adhesion Molecules Research
- Bacterial Genetics and Biotechnology
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Antibiotic Resistance in Bacteria
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- RNA Research and Splicing
- Signaling Pathways in Disease
- Redox biology and oxidative stress
- Protein Kinase Regulation and GTPase Signaling
- Peroxisome Proliferator-Activated Receptors
- Blood Coagulation and Thrombosis Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Metal-Catalyzed Oxygenation Mechanisms
- Advanced Proteomics Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
Linköping University
2015-2025
Thinfilm (Sweden)
2022
Karolinska Institutet
1995-2007
Lund University
1993-1996
Los Alamos National Laboratory
1996
The crucial role of Myc as an oncoprotein and a key regulator cell growth makes it essential to understand the molecular basis function. N-terminal region c-Myc coordinates wealth protein interactions involved in transformation, differentiation apoptosis. We have characterized detail intrinsically disordered properties Myc-1–88, where hierarchical phosphorylation S62 T58 regulates activation destruction protein. By nuclear magnetic resonance (NMR) chemical shift analysis, relaxation...
Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers. The condition is often fatal and the majority live-born children require a pacemaker at an early age. specific antibody that induces mechanism by which it mediates pathogenic effect have not been elucidated. In this study, we define cellular leading to disease show maternal directed epitope within leucine zipper amino acid sequence 200–239 (p200) Ro52 protein correlate with...
Glutaredoxins are ubiquitous proteins that catalyze the reduction of disulfides via reduced glutathione (GSH). Escherichia coli has three glutaredoxins (Grx1, Grx2, and Grx3), all containing classic dithiol active site CPYC. We report cloning, expression, characterization a novel monothiol E. glutaredoxin, which we name glutaredoxin 4 (Grx4). The protein consists 115 amino acids (12.7 kDa), (CGFS) potential shows high sequence homology to other especially yeast Grx5. Experiments with gene...
Abstract The deubiquitinase (DUB) ubiquitin‐specific protease 14 (USP14) is a dual domain protein that plays regulatory role in proteasomal degradation and has been identified as promising therapeutic target. USP14 comprises conserved USP ubiquitin‐like (Ubl) separated by 25‐residue linker. enzyme activity of autoinhibited solution, but enhanced when bound to the proteasome, where Ubl domains bind Rpn1 Rpt1/Rpt2 units, respectively. No structure full‐length absence proteasome yet presented,...
Enhanced understanding of structure-function relationships human 21-hydroxylase, CYP21, is required to better understand the molecular causes congenital adrenal hyperplasia. To this end, a structural model CYP21 was calculated based on crystal structure rabbit CYP2C5. All but two known allelic variants missense type, total 60 disease-causing mutations and six normal variants, were analyzed using model. A explanation for corresponding phenotype found all mutants which available clinical data...
Coagulation factor X is a serine protease containing three noncatalytic domains: an N-terminal γ-carboxyglutamic acid (Gla)1 domain followed by two epidermal growth (EGF)-like domains. The isolated EGF binds Ca2+ with Kd of 10-3 M. When linked to the Gla domain, however, its affinity increased 10-fold. In this paper, we present NMR solution structure Gla−EGF pair bound as well small angle X-ray scattering (SAXS) data on and without Ca2+. Our results show that binding makes domains fold...
Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remain an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control phosphorylation, chromatin occupancy, stability, however molecular basis remains unclear. Here we demonstrate that interacts directly with through homology Box 0 (MB0), a highly conserved region recently shown be important for activity. By NMR identified distinct peptide motif within...
Abstract A large number of natural products have been advocated as anticancer agents. Many these compounds contain functional groups characterized by chemical reactivity. It is not clear whether distinct mechanisms action can be attributed to such compounds. We used a library screening approach demonstrate that substantial fraction (~20%) cytotoxic synthetic containing Michael acceptor inhibit proteasome substrate processing and induce cellular response characteristic inhibition. Biochemical...
Abstract Ubiquitin‐specific protease 14 (USP14) is a member of the USP family responsible for catalytic removal ubiquitin (Ub) from proteins directed to proteasome, implicated in pathogenesis neurodegeneration and cancer. Crystallography cryo‐EM analysis have identified loop regions crucial deubiquitinase activity USP14, specifically those involved Ub proteasome binding. However, structural changes USP14 upon ligand binding these are minimal, indicating significant yet uncharacterized...
The ubiquitous glutaredoxin protein family is present in both prokaryotes and eukaryotes, closely related to the thioredoxins, which reduce their substrates using a dithiol mechanism as part of cellular defense against oxidative stress. Recently identified monothiol glutaredoxins, must use different functional mechanism, appear be essential Escherichia coli yeast are well conserved higher order genomes. We have employed high resolution NMR determine three-dimensional solution structure...
Hydroxylation of aspartic acid to erythro-beta-aspartic (Hya) occurs in epidermal growth factor (EGF)-like modules numerous extracellular proteins with diverse functions. Several EGF-like the consensus sequence for hydroxylation bind Ca2+, and it has therefore been suggested that hydroxyl group is essential Ca2+ binding. To determine directly influence beta-hydroxylation on calcium binding from coagulation factors IX X, we have now measured both fully beta-hydroxylated non-beta-hydroxylated...
Disturbances in fatty acid metabolism are involved the etiology of insulin resistance and related dyslipidemia, hypertension, procoagulant state. The transport proteins (FATPs) implicated facilitated cellular uptake nonesterified acids (NEFAs), thus potentially regulating NEFA concentrations metabolism. aim this study was to investigate polymorphic loci FATP4 gene with respect associations fasting postprandial lipid lipoprotein variables markers 608 healthy, middle-aged Swedish men evaluate...