Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase

Cysteinyl leukotrienes are key mediators in inflammation and have an important role in acute and chronic inflammatory diseases of the cardiovascular and respiratory systems, in particular bronchial asthma. In the biosynthesis of cysteinyl leukotrienes, conversion of arachidonic acid forms the unstable epoxide leukotriene A4 (LTA4). This intermediate is conjugated with glutathione (GSH) to produce leukotriene C4 (LTC4) in a reaction catalysed by LTC4 synthase: this reaction is the key step in cysteinyl leukotriene formation. Here we present the crystal structure of the human LTC4 synthase in its apo and GSH-complexed forms to 2.00 and 2.15 A resolution, respectively. The structure reveals a homotrimer, where each monomer is composed of four transmembrane segments. The structure of the enzyme in complex with substrate reveals that the active site enforces a horseshoe-shaped conformation on GSH, and effectively positions the thiol group for activation by a nearby arginine at the membrane-enzyme interface. In addition, the structure provides a model for how the omega-end of the lipophilic co-substrate is pinned at one end of a hydrophobic cleft, providing a molecular 'ruler' to align the reactive epoxide at the thiol of glutathione. This provides new structural insights into the mechanism of LTC4 formation, and also suggests that the observed binding and activation of GSH might be common for a family of homologous proteins important for inflammatory and detoxification responses.     

'On Going Up in the World': Nation,Region and the Land Elevation Debate in Sweden

The aim of the article is to analyse the relationship between Quaternary geology, the idea of land elevation, nationalism and regionalism in Scandinavia, with special regard to the contribution of Swedish geologists at the end of the nineteenth century. From a scientific point of view, the idea of land elevation was connected to the acceptance of the glaciation theory and the elevation theory of Thomas F. Jamieson, but analysed in a wider cultural context it is possible to understand both the professionalization of Quaternary geology and the new theory of shore-line displacement as expressions of Swedish cultural nationalism. As a complement to the specific cultural history, the Quaternary geology enterprise was a way of constituting a unique natural history of the nation. One of the new theories that developed in this process was that of the Highest Marine Border, a complex concept established by the distinguished geologist Gerard De Geer at the end of the 1880s in order to defend the theory of land elevation, which was threatened by the work of Eduard Suess. The line was considered to be a geographical border that both expressed the elevation pattern and sharply divided Sweden into one part that had been covered by water during the post-glacial period and another part that had not. The study continues by looking more closely at the construction of the border in the north of Sweden. Through an account of a subsequent scientific dispute between De Geer and the geologist Arvid Gustaf Hogbom it is clear that the concept of the Highest Marine Border was shaped not only by nationalism but also by regionalism.     

Genetically engineered avidins and streptavidins

Chicken avidin and bacterial streptavidin, (strept)avidin, are proteins widely utilized in a number of applications in life science, ranging from purification and labeling techniques to diagnostics, and from targeted drug delivery to nanotechnology. (Strept)avidin-biotin technology relies on the extremely tight and specific affinity between (strept)avidin and biotin (dissociation constant, K_d≈10⁻¹⁴–10⁻¹⁶ M). (Strept)avidins are also exceptionally stable proteins. To study their ligand binding and stability characteristics, the two proteins have been extensively modified both chemically and genetically. There are excellent accounts of this technology and chemically modified (strept)avidins, but no comprehensive reviews exist concerning genetically engineered (strept)avidins. To fill this gap, we here go through the genetically engineered (strept)avidins, summarizing how these constructs were designed and how they have improved our understanding of the structural and functional characteristics of these proteins, and the benefits they have provided for (strept)avidin-biotin technology. Received 22 June 2006; received after revision 1 August 2006; accepted 21 September 2006     

Survival of bull spermatozoa after exposure to 150 atm N2 for 15 days

Zusammenfassung Bullenspermien überleben in N₂ bei 150 atm und + 6°C gut 8 Tage (bis 14 Tage). In H₂ bei 100 atm und + 6°C nimmt die Überlebensfähigkeit ab. An den Spermien wurden Schäden durch Entwicklung von Gasbläschen bei Drucksenkung beobachtet. Weitere Versuche bei höherem Druck sind in reiner Flüssigkeitsumgebung auszuführen.     

Three-dimensional structure of the free radical protein of ribonucleotide reductase

The enzyme ribonucleotide reductase furnishes precursors for the DNA synthesis of all living cells. One of its constituents, the free radical protein, has an unusual alpha-helical structure. There are two iron centres that are about 25 A apart in the dimeric molecule. Tyrosine 122, which harbours the stable free radical necessary for the activity of ribonucleotide reductase, is buried inside the protein and is located 5 A from the closest iron atom.     

关于停时的一个注记

对任意停时T,定义A(T)={停时S:S≤T,在{T>0}上S相似文献