Developments in the carotenoid field

Zusammenfassung Nach einleitender kurzer Würdigung der Höhepunkte derKarrer'schen Carotinoid-Forschung wird zunächst ein knapper Überblick über den gegenwärtigen Stand der Carotinoid-Forschung gegeben. Die jetzige Kenntnis von Biosynthese und Funktion der Carotinoid-Pigmente wird kurz und die organisch-chemischen Aspekte werden etwas ausführlicher erläutert, und zwar Strukturaufklärung einschliesslich neuer Trennmethoden, unentbehrliche spektroskopische Methoden und neue Reaktionen zur Herstellung von Derivaten sowie schliesslich die Totalsynthese.Anschliessend werden einige ausgewählte Beispiele der NachleseKarrer'scher Beiträge behandelt, nämlich Probleme, die vonKarrer aufgegriffen wurden oder auf andere Weise mitKarrer's Arbeit verbunden sind und später im Laboratorium der Autorin weiter verfolgt wurden. Beispiele von Carotinoiden aus photosynthetischen Bakterien, C₅₀-Carotinoiden, glycosidischen Carotinoiden und Nor-carotinoiden mit Ringverengung werden diskutiert.

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Based on a lecture delivered at the Paul Karrer Symposium on 18 April 1969 in Zürich. The original paper contained a more detailed review and evaluation of Karrer's direct contribution to carotenoid research.     

The N-terminal amino acid sequence of the small subunit of ribulose-1,5-diphosphate carboxylase fromNicotiana tabacum

Summary The N-terminal sequence of the small subunit of Fraction I protein isolated from tobacco was investigated, using an automatic protein sequencer. The amino acid sequence of the first 21 residues is presented.     

Chiral recognition in dimerization of adsorbed cysteine observed by scanning tunnelling microscopy

Stereochemistry plays a central role in controlling molecular recognition and interaction: the chemical and biological properties of molecules depend not only on the nature of their constituent atoms but also on how these atoms are positioned in space. Chiral specificity is consequently fundamental in chemical biology and pharmacology and has accordingly been widely studied. Advances in scanning probe microscopies now make it possible to probe chiral phenomena at surfaces at the molecular level. These methods have been used to determine the chirality of adsorbed molecules, and to provide direct evidence for chiral discrimination in molecular interactions and the spontaneous resolution of adsorbates into extended enantiomerically pure overlayers. Here we report scanning tunnelling microscopy studies of cysteine adsorbed to a (110) gold surface, which show that molecular pairs formed from a racemic mixture of this naturally occurring amino acid are exclusively homochiral, and that their binding to the gold surface is associated with local surface restructuring. Density-functional theory calculations indicate that the chiral specificity of the dimer formation process is driven by the optimization of three bonds on each cysteine molecule. These findings thus provide a clear molecular-level illustration of the well known three-point contact model for chiral recognition in a simple bimolecular system.     

Crystal structure of a copper-transporting PIB-type ATPase

Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 ? resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.     

Species-specific responses of Late Quaternary megafauna to climate and humans

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.     

Collaborative Regional Innovation Initiatives: A Booster for Local Company Innovation Processes?

It is widely acknowledged that the rate of innovations can be enhanced through interaction between new constellations of actors, crossing borderlines between different mindsets, knowledge and skill bases (e.g. Brown and Duguid, Org Sci 2(1):40–57, 1991; Cooke and Morgan, The associational economy: firms, regions, and innovation, 1998; Leonard-Barton, Wellsprings of knowledge: building and sustaining the sources of innovation, 1995, p. 64; Stamm, Managing innovation, design and creativity, 2008, p. 335). Studies of economic prosperity have also pointed to cooperation and competition between neighboring actors as a driver for competitiveness and innovativeness, be it for a company, a business area or a region (e.g. Piore and Sabel, The second industrial divide: possibilities for prosperity, 1984; Porter, The competitive advantage of nations, 1990). The hypothesis behind the geographical focus is that geographical proximity between actors promotes interaction and hence innovation. In EU, and also in Norway, this has been used actively as guidance in national and regional policy, where construction of innovation systems such as clusters and interorganizational networks are promoted and funded. To get organizations and institutions in a region to collaborate more is seen as the panacea for innovation, transformation and prosperity. However, companies often treat such constructed initiatives as an add-on to their ordinary, often long-lasting, business relationships between customers and suppliers (Håkansson et al., Business in networks, 2009, p. 13). This could imply that the necessary anchoring of such new innovation system initiatives with the companies’ own innovation processes is weak or missing. The terminology system points to the importance of the different elements (actors) in the system, their interrelatedness and their impact on each other (Meadows, Thinking in systems. A primer, 2009). An innovation system, like a network, cannot deliver innovation if the elements (i.e. the companies) of the systems don’t respond with related actions to the common endeavor. However, the different actors’ intraorganizational innovation processes are hardly mentioned in the innovation systems theories, thus lacking the important system feedback link between the intraorganizational innovation processes within the single company and the interorganizational innovation processes which are taking place in the collaborative initiative. In this article it is argued, supported by a case story, that attention to both of these processes and the nexus between them is needed in order to construct sustainable interorganizational innovation system initiatives. A model for this is proposed, based on a dual organization development process, encouraging system feedback loops and thereby bridging the single participating organization and the interorganizational collaborative initiative.     

Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry

The bacteria causing diphtheria, whooping cough, cholera and other diseases secrete mono-ADP-ribosylating toxins that modify intracellular proteins. Here, we describe four structures of a catalytically active complex between a fragment of Pseudomonas aeruginosa exotoxin A (ETA) and its protein substrate, translation elongation factor 2 (eEF2). The target residue in eEF2, diphthamide (a modified histidine), spans across a cleft and faces the two phosphates and a ribose of the non-hydrolysable NAD+ analogue, betaTAD. This suggests that the diphthamide is involved in triggering NAD+ cleavage and interacting with the proposed oxacarbenium intermediate during the nucleophilic substitution reaction, explaining the requirement of diphthamide for ADP ribosylation. Diphtheria toxin may recognize eEF2 in a manner similar to ETA. Notably, the toxin-bound betaTAD phosphates mimic the phosphate backbone of two nucleotides in a conformational switch of 18S rRNA, thereby achieving universal recognition of eEF2 by ETA.