8,768 research outputs found
Structural Characterization of OxyD, a Cytochrome P450 Involved in β−Hydroxytyrosine Formation in Vancomycin Biosynthesis
No full textThe cytochrome P450 OxyD from the balhimycin glycopeptide antibiotic biosynthetic operon of <i>Amycolatopsis mediterranei</i> is involved in the biosynthesis of the modified amino acid β−<i>R</i>−hydroxytyrosine, an essential precursor for biosynthesis of the vancomycin−type aglycone. OxyD binds the substrate tyrosine not free in solution, but rather covalently linked to the carrier protein (CP) domain of the non−ribosomal peptide synthase BpsD, exhibiting micromolar binding affinity to a tyrosine−loaded carrier protein construct. The crystal structure of OxyD was determined to 2.1−Å resolution, revealing a potential binding site for the carrier protein−bound substrate in a different orientation to that seen with the acyl carrier protein−bound P450BioI (Cryle, M. J., and Schlichting, I. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 15696−15701). A series of residues were identified across known aminoacyl−CP−oxidizing P450s that are highly conserved and cluster in the active site or potential CP binding site of OxyD. These residues appear to be characteristic for aminoacyl−CP−oxidizing P450s, allowing sequence based identification of P450 function for this subgroup of P450s that play vital roles in the biosyntheses of many important natural products in addition to the vancomycin−type antibiotics. The ability to analyze such P450 function based upon sequence data alone should prove an important tool in the analysis and identification of new medicinally relevant biomolecules
Structural and Biochemical Characterization of the Cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: A Cyclo-l-leucyl-l-leucyl Dipeptide Oxidase
No full textCytochrome P450 CypX (CYP134A1), isolated from Bacillus subtilis, has previously been implicated in the three-step oxidative transformation of the diketopiperazine cyclo-l-leucyl-l-leucyl into pulcherriminic acid, a precursor of the extracellular iron chelate pulcherrimin. In this study, we present the first experimental data relating to CYP134A1, where we show that CYP134A1 binds cyclo-l-leucyl-l-leucyl with an affinity of 24.5 +/- 0.5 muM. Structurally related diketopiperazines sharing similar alkyl side chains to cyclo-l-leucyl-l-leucyl also bind to CYP134A1 with comparable affinity. CYP134A1 is capable of catalyzing the in vitro oxidation of diketopiperazine substrates when supported with several alternate electron transfer partner systems. Products containing one additional oxygen atom and which are intermediate products of the expected pulcherriminic acid were identified by GCMS. The oxidation of related diketopiperazines reveals that different oxidative pathways exist for CYP134A1-catalyzed diketopiperazine oxidation. The crystal structure of CYP134A1 has been determined to 2.7 A resolution in the absence of substrate and in the presence of bound phenylimidazole ligands to 3.1 and 3.2 A resolution. The active site is dominated by hydrophobic residues and contains an unusual proline residue in place of the normally conserved alcohol residue that typically plays an important role in oxygen activation. The B-B(2) substrate recognition loop, which forms part of the active site, shows considerable flexibility and was found in both open and closed conformations in different structures. These results represent the first insights into the structural and biochemical basis underlying the multistep oxidation catalyzed by CYP134A1.Max J. Cryle, Stephen G. Bell, and Ilme Schlichtin
Enseñanza de la escritura de Max Aub: comprensión y memoria
No full textEste texto analiza a obra testimonial de Max Aub sobre su experiencia en los campos de concentración en Francia desde una perspectiva de discursos comparados. Para destacar las estrategias de la escritura del autor recuperables por otros proyectos discursivos que persigan la sensibilización y la denuncia a través del cruce entre la comunicación y la éticaThis text analyses the testimonial work of Max Aub about his experience in the French concentration camps in France from comparative discourses approach. It emphasizes the writing strategies used by the author useful for other awareness and denounce discourses through the dialogue among communication and ethic
Carrier protein substrates in cytochrome P450−catalysed oxidation
No full textEnzymes of the cytochrome P450 superfamily can catalyse many types of oxidative transformations of a diverse substrate range. This review summarises recent work on an subset of P450s that accept their substrates in carrier protein−bound form. These examples show how the oxidative power and precision that P450s bring to natural products biosynthesis can be coupled with the advantages of using a carrier protein as a scaffold for oxidatio
Max Brooks literary reading flier
No full text2012 Bismarck State College Visiting Writers Series and ArtsQuest present: Max Brooks. April 25, 7:30 p.m.; Belle Mehus Auditorium. Max Brooks is the author of World War Z: An Oral History of the Zombie War and the graphic novel The Zombie Survival Guide: Recorded Attacks
Selectivity in a barren landscape: the P450BioI−ACP complex
No full textThe cytochromes P450 (P450s) are a superfamily of oxidative haemoproteins that are capable of catalysing a vast range of oxidative transformations, including the oxidation of unactivated alkanes, often with high stereo− and regio−selectivity. Fatty acid hydroxylation by P450s is widespread across both bacteria and higher organisms, with the sites of oxidation and specificity of oxidation varying from system to system. Several key examples are discussed in the present article, with the focus on P450BioI (CYP107H1), a biosynthetic P450 found in the biotin operon of <i>Bacillus subtilis</i>. The biosynthetic function of P450BioI is the formation of pimelic acid, a biotin precursor, via a multiple−step oxidative cleavage of long−chain fatty acids. P450BioI is a member of an important subgroup of P450s that accept their substrates not free in solution, but rather presented by a separate carrier protein. Structural characterization of the P450BioI−ACP (acyl−carrier protein) complex has recently been performed, which has revealed the basis for the oxidation of the centre of the fatty acid chain. The P450BioI−ACP structure is the first such P450−carrier protein complex to be characterized structurally, with important implications for other biosynthetically intriguing P450−carrier protein complexes
Max Frisch's novel: Stiller. A study
No full text The attempt is made in the following study to present an interpretation of the novel "Stiller" by the Swiss author, Max Frisch, by tracing through the novel the dominant themes of the graven-image or 'Bildnis' and that of the problem of freedom with reference to the novel's main character. ThesisMaster of Arts (MA
A Transfer Report on the Development of a Framework to Evaluate Search Interfaces for their Support of Different User Types and Search Tactics
No full textAs the understanding of search systems, user needs and seeking strategies is developing, the design of search user interfaces is evolving to support more complicated and exploratory forms of search. With the design of new search features that enable these richer modes of exploration, comes the need to better understand the support they provide. In this report a new evaluation framework is presented that analyses search features for how they a) contribute to an overall interface, b) allow users to carry out different search tactics, and c) support different types of users and their needs. The novel contributions of the framework improve on some of the limitations of typical user studies, and allow search systems to be systematically analysed in much more detail and in much less time. The presented evaluation framework is then validated in three ways. First the validity of the models used as the building blocks of the framework are investigated through related work. Second the method of integrating these building-block models is validated and strengthened by consensus of expert opinion. Third, the overall approach is validated by comparing its analyses to the results of previously carried out user studies. The validation process has shown both the value of the framework and identified areas of future work that should be addressed for the framework to be completed. This report concludes with the set of contributions that the framework makes, and why the remaining work will be challenging, but critical to the final design
The subzero microbiome: Microbial activity in frozen and thawing soils
No full textMost of the Earth's biosphere is characterized by low temperatures (<5 °C) and cold-adapted microorganisms are widespread. These psychrophiles have evolved a complex range of adaptations of all cellular constituents to counteract the potentially deleterious effects of low kinetic energy environments and the freezing of water. Microbial life continues into the subzero temperature range, and this activity contributes to carbon and nitrogen flux in and out of ecosystems, ultimately affecting global processes. Microbial responses to climate warming and in particular, thawing of frozen soils are not yet well understood although the threat of microbial contribution to positive feedback of carbon flux is substantial. To date, several studies have examined microbial community dynamics in frozen soils and permafrost due to changing environmental conditions, and some have undertaken the complicated task of characterizing microbial functional groups and how their activity changes with changing conditions, either in situ or by isolating and characterizing macromolecules. With increasing temperature and wetter conditions microbial activity of key microbes and subsequent efflux of greenhouse gases also increase. In this review, we aim to provide an overview of microbial activity in seasonally frozen soils and permafrost. With a more detailed understanding of the microbiological activities in these vulnerable soil ecosystems, we can begin to predict and model future expectations for carbon release and climate change.Peer reviewe
Frontline Timor : to resist is to win. by Max Stahl
No full texttag=1 data=Frontline Timor : to resist is to win. by Max Stahl
tag=2 data=Stahl, Max
tag=3 data=The Australian Magazine,
tag=6 data=18/19 January 1992
tag=7 data=6-12.
tag=8 data=SOUTH-EAST ASIA
tag=9 data=EAST TIMOR
tag=10 data=The author describes a rarely permitted visit to the secret camps of the Timorese guerillas who, despite the Dili massacre and the crushing presence of the Indonesian military, continue to hold out and plot for independence.
tag=11 data=1992/4/2
tag=12 data=92/0116
tag=13 data=CABThe author describes a rarely permitted visit to the secret camps of the Timorese guerillas who, despite the Dili massacre and the crushing presence of the Indonesian military, continue to hold out and plot for independence
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