Publications by authors named "Erlandsen H"
Article Synopsis
- UBE3A/E6AP expression abnormalities are linked to neurological disorders like Angelman syndrome and autism, with three protein isoforms existing that have unique functions and cellular roles.
- Research shows the isoforms differ structurally, particularly in their N-terminal regions, affecting their ability to bind to the proteasome and multimerize, which is crucial for their proper activation.
- Advanced techniques, including NMR spectroscopy, reveal that some isoforms have dynamic features that could influence their response to oxidative stress, enhancing the understanding of UBE3A's functions and potential therapeutic targets for related disorders.
Covalent labeling of therapeutic drugs and proteins with polyethylene glycol (PEGylation) is an important modification for improving stability, solubility, and half-life. PEGylation alters protein solution behavior through its impact on thermodynamic nonideality by increasing the excluded volume, and on hydrodynamic nonideality by increasing the frictional drag. To understand PEGylation's impact, we investigated the thermodynamic and hydrodynamic properties of a model system consisting of PEGylated human serum albumin derivatives using analytical ultracentrifugation (AUC) and dynamic light scattering (DLS).
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- PML protein is crucial for how cells respond to oxidative stress, but its specific mechanism is not well understood.
- Researchers found that the B-box1 domain of PML is more sensitive to oxidative changes compared to the RING domain.
- This sensitivity enhances PML's ability to form nuclear bodies in cells, indicating B-box1 is a key player in detecting oxidative stress.
Article Synopsis
- Translesion synthesis (TLS) DNA polymerase Polζ, particularly its Rev7 subunit, is vital for DNA damage bypass during replication, working with Rev3 and Rev1.
- Human Rev7 forms a stable head-to-head dimer with Rev3 through a mechanism typical of HORMA proteins, while yeast Rev7 (scRev7) forms an asymmetric head-to-tail dimer with a significantly smaller bonding interface.
- Biophysical studies suggest that scRev7 does not dimerize in solution by itself or through its binding to Rev3, indicating that the dimerization seen in structures is likely due to interactions with other Polζ subunits, suggesting evolutionary changes in the dimerization mechanism.
Article Synopsis
- Two isoforms of dihydrofolate reductase (DHFR), DfrA1 and DfrA5, found in Gram-negative bacteria were studied to understand their resistance to trimethoprim (TMP) and help develop new antibiotics.
- Preliminary tests on new antifolate compounds showed that they effectively inhibit DHFR in both Escherichia coli and the DfrA isoforms.
- The researchers utilized crystal structures of DHFR bound to TMP and novel antifolates to identify key binding pocket features, aiding in the design of broad-spectrum DHFR inhibitors.
Article Synopsis
- The study investigates how oncogenic C-terminal binding Protein (CtBP) activates and assembles in response to NAD(H) binding, focusing on its behavior as either dimers or tetramers.
- Using ultracentrifugation, researchers confirmed that CtBP forms tetramers when bound to NAD or NADH, with specific dissociation constants indicating the strength of this assembly.
- Isothermal titration calorimetry revealed varying dissociation constants for NAD(H) binding to CtBP, suggesting that under normal cellular conditions, CtBP is fully occupied by NAD and might not effectively sense NADH levels.
Background: Reversible enzymatic methylation of mammalian mRNA is widespread and serves crucial regulatory functions, but little is known to what degree chemical alkylators mediate overlapping modifications and whether cells distinguish aberrant from canonical methylations.
Methods: Here we use quantitative mass spectrometry to determine the fate of chemically induced methylbases in the mRNA of human cells. Concomitant alteration in the mRNA binding proteome was analyzed by SILAC mass spectrometry.
Article Synopsis
- SF2312 is a natural antibiotic produced by the actinomycete Micromonospora, showing effectiveness against various bacteria by inhibiting human enolase.
- Recent research explored how SF2312 binds to E. coli enolase, revealing it mimics an important intermediate in enzyme activity, making it a strong inhibitor.
- The combination of SF2312 with fosfomycin, particularly alongside glucose-6 phosphate, shows significant synergy, indicating their potential as an effective treatment strategy targeting different bacterial mechanisms.
The RNA-activated protein kinase, PKR, is a key mediator of the innate immunity response to viral infection. Viral double-stranded RNAs induce PKR dimerization and autophosphorylation. The PKR kinase domain forms a back-to-back dimer.
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- The study highlights the potential of using metal-ligand interactions to control protein complex formation, which is important for developing advanced biomaterials.
- The researchers designed three protein dimers that are monomeric without metal and form stable dimers when zinc sulfate is present, emphasizing their high-affinity and symmetric characteristics.
- The dimers exhibit notable thermal stability and can dissociate in the presence of EDTA, with structural analysis confirming effective zinc binding and desired dimer configurations.
The folate biosynthetic pathway offers many druggable targets that have yet to be exploited in tuberculosis therapy. Herein, we have identified a series of small molecules that interrupt Mycobacterium tuberculosis (Mtb) folate metabolism by dual targeting of dihydrofolate reductase (DHFR), a key enzyme in the folate pathway, and its functional analog, Rv2671. We have also compared the antifolate activity of these compounds with that of para-aminosalicylic acid (PAS).
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- Enolase is an important enzyme in glycolysis that plays key roles in cell processes like cell wall formation and RNA turnover, making it a valuable target for antibacterial drug development.
- Researchers used a DARTS assay to identify enolase in Escherichia coli and tested various tropolone derivatives for their antibacterial activity against multiple Gram-negative strains, discovering that α- and β-substituted compounds were the most effective.
- Further investigations demonstrated that these tropolone derivatives inhibit enolase’s catalytic activity and the findings suggest that the structure of these compounds significantly influences their antibacterial effectiveness.
Footpad dermatitis is a condition that causes lesions on the plantar surface of the footpads in growing turkeys. Potential inflammatory processes and pain associated with increasing severity of footpad dermatitis raise animal welfare concerns. This study investigated whether the temperature of the plantar surface of the foot (the footpads and the entire plantar foot including interdigital membranes) assessed with infrared thermography reflects severity of mild footpad dermatitis as assessed with a Visual Analogue Scale in 80 turkey toms at 10 weeks of age.
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- Singleton-Merten syndrome (SMS) is a rare genetic disorder with symptoms like severe aortic calcification, dental issues, and bone problems.
- Researchers found a specific mutation in the IFIH1 gene linked to this syndrome in affected families, which is also associated with some autoimmune diseases.
- The mutation seems to enhance the function of MDA5 protein, leading to increased immune response and early onset of the syndrome's symptoms.
More than 33,000 glycosyltransferases have been identified. Structural studies, however, have only revealed two distinct glycosyltransferase (GT) folds, GT-A and GT-B. Here we report a 1.
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- Pleiotrophin (PTN) is a key growth factor involved in the recruitment and differentiation of osteoblasts, but little is known about its role during tooth development.
- Researchers conducted experiments using various mouse dental cell lines and analyzed PTN expression through multiple techniques, including immunocytochemistry and PCR.
- Findings revealed that PTN is consistently expressed in dental cell lines and is influenced by bone morphogenetic proteins, particularly at different stages of maturation in ameloblasts and odontoblasts during tooth formation.
Serine-rich repeat glycoproteins (SRRPs) are a growing family of bacterial adhesins found in many streptococci and staphylococci; they play important roles in bacterial biofilm formation and pathogenesis. Glycosylation of this family of adhesins is essential for their biogenesis. A glucosyltransferase (Gtf3) catalyzes the second step of glycosylation of a SRRP (Fap1) from an oral streptococcus, Streptococcus parasanguinis.
View Article and Find Full Text PDFExpression, purification, crystallization and preliminary X-ray analysis of ORF60, the small subunit (R2) of ribonucleotide reductase from Kaposi's sarcoma-associated herpesvirus (KSHV).
Acta Crystallogr Sect F Struct Biol Cryst Commun
June 2010
Article Synopsis
- Ribonucleotide reductase (RNR) converts ribonucleotides into deoxyribonucleotides, essential for DNA synthesis and is found in all life forms and some large DNA viruses.
- The alpha and gamma herpesviruses possess two active RNR subunits, while beta herpesviruses only have an inactive one.
- The text discusses the successful crystallization of the R2 subunit from Kaposi's sarcoma-associated gamma-herpesvirus (KSHV), detailing the methods used and the characteristics of the crystals obtained, including their resolution and structure.
The Kaposi's sarcoma-associated herpesvirus protein SOX (shut off and exonuclease) and its Epstein-Barr virus homolog, BGLF5, are active during the early lytic phase and belong to the alkaline nuclease family. Both proteins have been shown to be bifunctional, being responsible for DNA maturation as well as host shutoff at the mRNA level. We present the crystal structure of SOX determined at 1.
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- YhaK is a protein found in low amounts in E. coli, shown to be up-regulated by nitroso-glutathione and during biofilm growth in human urine.
- The protein features a unique bicupin structure with specific cysteine oxidation and chloride ions, which may indicate a role in oxidative stress response.
- Unlike similar proteins, YhaK lacks typical metal-binding properties and does not display common enzymatic activities, suggesting a new subclass of bicupins potentially involved in oxidative stress sensing.
Article Synopsis
- Nucleotide methylations are common rRNA modifications in bacteria, with YebU methylating a specific site (C1407) on the 16 S rRNA in Escherichia coli.
- YebU requires S-adenosyl-l-methionine (SAM) to function and has a unique three-dimensional structure revealed by X-ray crystallography, which includes similarities to other methyltransferases and an unexpected PUA domain.
- The interaction of YebU with the 30 S ribosomal subunit involves multiple contacts with the rRNA and ribosomal protein S12, explaining its specificity for assembled ribosomes over naked rRNA.
Phenylketonuria patients harboring a subset of phenylalanine hydroxylase (PAH) mutations have recently shown normalization of blood phenylalanine levels upon oral administration of the PAH cofactor tetrahydrobiopterin [(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4)]. Several hypotheses have been put forward to explain BH4 responsiveness, but the molecular basis for the corrective effect(s) of BH4 has not been understood. We have investigated the biochemical, kinetic, and structural changes associated with BH4-responsive mutations (F39L, I65T, R68S, H170D, E178G, V190A, R261Q, A300S, L308F, A313T, A373T, V388M, E390G, P407S, and Y414C).
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- A specific type of phenylalanine hydroxylase (PAH) deficiency linked to PKU mutations shows responsiveness to BH4 supplementation, but the exact molecular reasons for this are not yet clear.
- Researchers analyzed the kinetic and cofactor binding properties of recombinant human PAH and various mild PKU mutations expressed in E. coli, finding that all mutations caused catalytic defects and some showed reduced BH4 binding affinity.
- BH4 not only increased PAH activity but also acted as a chemical chaperone, helping to stabilize proteins and prevent their degradation, suggesting that the response to BH4 treatment in PKU could involve multiple mechanisms.
Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by phenylalanine hydroxylase (PAH) deficiency. Dietary treatment has been the cornerstone for controlling systemic phenylalanine (Phe) levels in PKU for the past 4 decades. Over the years, it has become clear that blood Phe concentration needs to be controlled for the life of the patient, a difficult task taking into consideration that the diet becomes very difficult to maintain.
View Article and Find Full Text PDFAbout two-thirds of all mild phenylketonuria (PKU) patients are tetrahydrobiopterin (BH4)-responsive and thus can be potentially treated with BH4 instead of a low-phenylalanine diet. Although there has been an increase in the amount of information relating to the diagnosis and treatment of this new variant of PKU, very little is know about the mechanisms of BH4-responsiveness. This review will focus on laboratory investigations and possible molecular and structural mechanisms involved in this process.
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