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LukGH (LukAB) is a potent leukocidin of Staphylococcus aureus that lyses human phagocytic cells and is thought to contribute to immune evasion. Unlike the other bi-component leukocidins of S. aureus, LukGH forms a heterodimer before binding to its receptor, CD11b expressed on professional phagocytic cells, and displays significant sequence variation. We employed a high diversity human IgG1 library
Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches are not generally effective in most malignancies. Compounds such as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce differentiation in experimental systems, but their mechanisms of action and potential range of uses on that basis have not been developed. Here, we sho
The bi-component leukocidins of Staphylococcus aureus are important virulence factors that lyse human phagocytic cells and contribute to immune evasion. The γ-hemolysins (HlgAB and HlgCB) and Panton-Valentine leukocidin (PVL or LukSF) were shown to assemble from soluble subunits into membrane-bound oligomers on the surface of target cells, creating barrel-like pore structures that lead to cell lys
Ribonucleotide reductases (RNRs) catalyze all new production in nature of deoxyribonucleotides for DNA synthesis by reducing the corresponding ribonucleotides. The reaction involves the action of a radical that is produced differently for different classes of the enzyme. Class I enzymes, which are present in eukaryotes and microorganisms, use an iron center to produce a stable tyrosyl radical that
Ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides. Three classes have been identified, all using free- radical chemistry but based on different cofactors. Classes I and II have been shown to be evolutionarily related, whereas the origin of anaerobic class III has remained elusive. The structure of a class III enzyme suggests a common origin for the three c
The R2 protein of ribonucleotide reductase catalyzes the dioxygen- dependent one-electron oxidation of Tyr122 at a diiron-carboxylate site. Methane monooxygenase and related hydroxylases catalyze hydrocarbon hydroxylation at diiron sites structurally related to the one in R2. In protein R2, the likely reaction site for dioxygen is close to Phe208. The crystal structure of an iron ligand mutant R2,
The tRNA glycylation system is amongst the most complex aminoacylation systems since neither the oligomeric structure of the enzymes nor the discriminator base in tRNAs are conserved in the phylae. To understand better this structural diversity and its functional consequences, the prokaryotic glycylation system from Thermus thermophilus, an extreme thermophile, was investigated and its structural
Reconstitution of the tyrosyl radical in ribonucleotide reductase protein R2 requires oxidation of a diferrous site by oxygen. The reaction involves one externally supplied electron in addition to the three electrons provided by oxidation of the Tyr-122 side chain and formation of the μ-oxo- bridged diferric site. Reconstitution of R2 protein Y122F, lacking the internal pathway involving Tyr-122,
Ribonucleotide reductase contains a stable organic free radical essential for its activity located on a tyrosine residue in the small subunit of the enzyme called R2. The substrate binding site is, however, found in the catalytic subunit called R1. A long-range protein-mediated radical transfer pathway appears to be responsible for the delivery of the radical from the tyrosine in R2 to the substra
Background: Ribonucleotide reductases (RNRs) catalyze the formation of the deoxyribonucleotides that are essential for DNA synthesis. The R2 subunit of Escherichia coli RNR is a homodimer containing one dinuclear iron centre per monomer. A tyrosyl radical is essential for catalysis, and is formed via a reaction in which the reduced, diferrous form of the iron centre activates dioxygen. To help und
Background: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O1BFS whose structure is known. Results The two new structures are, like O1BFS, both serotype O vi
The sequence and crystal structure at 2.75 Å resolution of the homodimeric glycyl-tRNA synthetase from Thermus thermophilus, the first representative of the last unknown class II synthetase subgroup, have been determined. The three class II synthetase sequence motifs are present but the structure was essential for identification of motif 1, which does not possess the proline previously believed to
The glycyl-tRNA synthetase from Thermus thermophilus is a dimer of molecular mass 115 kDa, which has been crystallised using the vapour diffusion method from 5 to 7% polyethylene glycol 6000, 0.8 to 1.4 M NaCl at protein concentrations of 2 to 8 mg/ml. Nucleation is carried out at 4°C and crystals are subsequently transferred to 15°C to maximise growth. Crystals are truncated rhombohedra measuring
Foot-and-mouth disease viruses from serotypes O, A and C have been crystallized. The particular strains studied include O1K, A1061, A22 Iraq 24/64, A24 Cruzeiro and C-S8c1. In addition, crystals have been grown of G67, a monoclonal antibody neutralization escape mutant derived from O1K, and of virus R100, recovered after the establishment of a persistent infection in baby hamster kidney cells with
Accumulating evidence suggests that individuals with greater executive resources spend less time mind wandering.Independent strands of research further suggest that this association depends on concentration and a guiltydysphoricdaydreaming style. However, it remains unclear whether this association is specific to particular featuresof executive functioning or certain operationalizations of mind wa
Smartphones and social media have become inextricable parts of our daily lives. The everyday lives and communication practices of migrant workers are particularly affected by these global technological developments. Such global developmental trends are especially visible within the growing body of scholarly literature on migrant transnationalism and technology, where mobile phones are examined as
Kopplingen mellan religion och dans i äldre tid, från antiken och medeltiden fram till tidigmodern tid i Europa.
Kakor och framväxten av bakverk till vardags från 1500-/1600-talet fram till sekelskiftet 1900.
Portraying Unease critically discusses a tendency amongst politicized scholars to endow artworks with traits of subversion and political productivity. Artworks that address structural discrimination, such as heterosexism, racism, or ableism, are often described as possessing qualities that can challenge unjust systems or initiate political change. This thesis considers hope and belief in the polit
Parkinson's disease (PD) is characterized by dopaminergic (DA) neuron loss and the formation of cytoplasmic protein inclusions. Although the exact pathogenesis of PD is unknown, iron dyshomeostasis has been proposed as a potential contributing factor. Emerging evidence suggests that glial cell activation plays a pivotal role in ferroptosis and subsequent neurodegeneration. We review the associatio
