9 research outputs found

    The Contribution of Coevolving Residues to the Stability of KDO8P Synthase

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    The evolutionary tree of 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase (KDO8PS), a bacterial enzyme that catalyzes a key step in the biosynthesis of bacterial endotoxin, is evenly divided between metal and non-metal forms, both having similar structures, but diverging in various degrees in amino acid sequence. Mutagenesis, crystallographic and computational studies have established that only a few residues determine whether or not KDO8PS requires a metal for function. The remaining divergence in the amino acid sequence of KDO8PSs is apparently unrelated to the underlying catalytic mechanism.The multiple alignment of all known KDO8PS sequences reveals that several residue pairs coevolved, an indication of their possible linkage to a structural constraint. In this study we investigated by computational means the contribution of coevolving residues to the stability of KDO8PS. We found that about 1/4 of all strongly coevolving pairs probably originated from cycles of mutation (decreasing stability) and suppression (restoring it), while the remaining pairs are best explained by a succession of neutral or nearly neutral covarions.Both sequence conservation and coevolution are involved in the preservation of the core structure of KDO8PS, but the contribution of coevolving residues is, in proportion, smaller. This is because small stability gains or losses associated with selection of certain residues in some regions of the stability landscape of KDO8PS are easily offset by a large number of possible changes in other regions. While this effect increases the tolerance of KDO8PS to deleterious mutations, it also decreases the probability that specific pairs of residues could have a strong contribution to the thermodynamic stability of the protein

    Ion-assisted deposition processes: Industrial network IntIon

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    The presented work is embedded in the research network "Integrative Ion Processes for Modern Optics", called IntIon, consisting of 12 partners from the German optics industry and two research institutes. The main target of the IntIon network is the development of new process concepts on the basis of ion assisted deposition (IAD) for the industrial production of optical thin film components. Besides an improvement in efficiency, a major aim is concentrated on the optical characteristics for selected application fields with high economical potential. In this network, different ion and plasma sources are compared with regard to their qualification for ion assisted deposition processes. This work includes the characterization of the ion energy and ion current using Faraday-cup measurements. The selection of investigated coating materials includes a broad variety of standard and non-standard oxides. First results of the network will be presented for adapted deposition materials and different operation characteristics of ion sources

    Current progress in innovative engineered antibodies

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    A Review of PCSK9 Inhibitors and their Effects on Cardiovascular Diseases

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