A5044932441- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Protease and Inhibitor Mechanisms
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Neuropeptides and Animal Physiology
- Protein Hydrolysis and Bioactive Peptides
- Mass Spectrometry Techniques and Applications
- Cellular Mechanics and Interactions
- Cardiac Structural Anomalies and Repair
- Aquaculture Nutrition and Growth
- Polyamine Metabolism and Applications
- Ferrocene Chemistry and Applications
- Biochemical Analysis and Sensing Techniques
- Sirtuins and Resveratrol in Medicine
- Enzyme Catalysis and Immobilization
- Cell Adhesion Molecules Research
- Chemical Synthesis and Analysis
University of Bergen
2015-2024
NORCE Norwegian Research Centre
2023-2024
Haukeland University Hospital
2015-2016
N-terminal (Nt) acetylation is a major protein modification catalyzed by acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated NatB in all eukaryotes, but animal actins containing additionally posttranslationally NAA80. Actin was found to regulate cytoskeletal dynamics and motility, thus making NAA80 potential target for cell migration regulation. In this work, we developed potent selective bisubstrate inhibitors determined the crystal...
About 80% of human proteins are amino-terminally acetylated (Nt-acetylated) by one seven Nt-acetyltransferases (NATs). Actin, the most abundant protein in cytoplasm, has its own dedicated NAT, NAA80, which acts posttranslationally and affects cytoskeleton assembly cell motility. Here, we show that NAA80 does not associate with filamentous actin cells, natural substrate is monomeric actin-profilin complex, consistent Nt-acetylation preceding polymerization. Nt-acetylates much more efficiently...
N-terminal acetylation, catalysed by acetyltransferases (NATs), is among the most common protein modifications in eukaryotes and involves transfer of an acetyl group from acetyl-CoA to α-amino first amino acid. Functions acetylation include degradation sub-cellular targeting. Recent findings humans indicate that a dysfunctional Nα-acetyltransferase (Naa) 10, catalytic subunit NatA, major NAT, associated with lethality during infancy. In present study, we identified Danio rerio orthologue...
Abstract Protein N-terminal (Nt) acetylation is one of the most abundant modifications in eukaryotes, covering ~50-80 % proteome, depending on species. Cells with defective Nt-acetylation display a wide array phenotypes such as impaired growth, mating defects and increased stress sensitivity. However, pleiotropic nature these effects has hampered our understanding functional impact protein Nt-acetylation. The main enzyme responsible for throughout eukaryotic kingdom acetyltransferase NatA....
N-terminal acetylation is a common protein modification in human cells and catalysed by acetyltransferases (NATs), mostly cotranslationally. The NAA10-NAA15 (NatA) complex the major NAT, responsible for acetylating ~ 40% of proteins. Recently, NAA10 germline variants were found patients with X-linked lethal Ogden syndrome, other familial or de novo cases variable degrees developmental delay, intellectual disability (ID) cardiac anomalies. Here we report novel (NM_003491.3) c.248G > A,...
NAA10 is the catalytic subunit of major N-terminal acetyltransferase complex NatA which acetylates almost half human proteome. Over past decade, many missense variants have been reported as causative genetic disease in humans. Individuals harboring often display variable degrees intellectual disability (ID), developmental delay, and cardiac anomalies. Initially, carrier females appeared to be oligo- or asymptomatic with X-inactivation pattern skewed towards wild type allele. However,...
The actin cytoskeleton is of profound importance to cell shape, division, and intracellular force generation. Profilins bind globular (G-)actin regulate filament formation. Although profilins are well-established regulators, the distinct roles dominant profilin, profilin 1 (PFN1),
Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, acetylation, catalyzed NAA80 humans. acetylation actin crucial for maintaining normal cytoskeletal dynamics cell motility human lines. However, physiological impact remains to be fully understood. We developed zebrafish
Protein hydrolysates made from marine by-products are very nutritious but frequently contain trimethylamine (TMA), which has an unattractive fish-like smell. Bacterial monooxygenases can oxidize TMA into the odorless N-oxide (TMAO) and have been shown to reduce levels in a salmon protein hydrolysate. To make flavin-containing monooxygenase (FMO) Methylophaga aminisulfidivorans (mFMO) more suitable for industrial application, we engineered it using Repair One-Stop Shop (PROSS) algorithm. All...
Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) the major acetyltransferase, with 40-50% all mammalian proteins being potential substrates. However, overall role amino-terminal on whole-organism level poorly understood, particularly in mammals. Male mice lacking show no globally apparent vivo impairment do not exhibit complete embryonic lethality. Rather nulls display increased neonatal lethality,...
Abstract Protein N-terminal (Nt) acetylation is one of the most abundant modifications in eukaryotes, covering ∼50-80 % proteome, depending on species. Cells with defective Nt-acetylation display a wide array phenotypes such as impaired growth, mating defects and increased stress sensitivity. However, pleiotropic nature these effects has hampered our understanding functional impact protein Nt-acetylation. The main enzyme responsible for throughout eukaryotic kingdom acetyltransferase NatA....
Abstract Actin is a key component of the cytoskeleton eukaryotic cells and involved in numerous cellular functions. In animal cells, actins are uniquely N-terminally processed by dedicated enzyme machinery to generate their mature acidic acetylated forms. The final step this maturation process involves N-terminal acetylation, reaction catalyzed NAA80 humans. human cell lines, acetylation actin plays crucial role maintaining normal cytoskeletal dynamics motility. physiological impact remains...
The majority of the human proteome is subjected to N-terminal (Nt) acetylation catalysed by acetyltransferases (NATs). NatA complex composed two core subunits—the catalytic subunit NAA10 and ribosomal anchor NAA15. Furthermore, may also have non-catalytic roles independent NatA. Several inherited de novo variants been associated with genetic disease in humans. In this study, we present a functional analysis variants, c.29A>G p.(D10G) c.32T>G p.(L11R), previously identified male female,...
NAA10 is a major N-terminal acetyltransferase (NAT) that catalyzes the cotranslational (Nt-) acetylation of 40% human proteome. Several reports lysine (KAT) activity by exist, but others have not been able to find any NAA10-derived KAT activity, latter which supported structural studies. The towards hypoxia-inducible factor 1α (HIF-1α) was recently found depend on hydroxylation at Trp38 inhibiting HIF-1α (FIH). In contrast, we could detect in several cell lines and no evidence interacts with...
Abstract The actin cytoskeleton is of profound importance to cell shape, division, and intracellular force generation. Profilins bind globular (G-)actin regulate filament formation. Although profilins are well-established regulators, the distinct roles dominant profilin, profilin 1 (PFN1), versus less abundant 2 (PFN2) remain enigmatic. Here, we define a specific role for PFN2 as stable interactor regulator N-terminal acetyltransferase NAA80. binding increases intrinsic catalytic activity...
Abstract Protein hydrolysates made from marine by-products are very nutritious, but frequently contain trimethylamine (TMA) which has an unattractive fish-like smell. Bacterial monooxygenases can oxidize TMA into the odorless N -oxide (TMAO) and have been shown to reduce TMA-levels in a salmon protein hydrolysate. To make Methylophaga aminisulfidivorans monooxygenase, mFMO, more suitable for industrial application, we engineered it using Repair One-Stop Shop (PROSS) algorithm. All seven...
Abstract Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) the major acetyltransferase, with 40-50% all mammalian proteins being potential substrates. However, overall role amino-terminal on whole-organism level poorly understood, particularly in mammals. Male mice lacking show no globally apparent vivo impairment do not exhibit complete embryonic lethality. Rather nulls display increased neonatal...