Structural and evolutionary relationships among protein tyrosine phosphatase domains

With the current access to the whole genomes of various organisms and the completion of the first draft of the human genome, there is a strong need for a structure-function classification of protein families as an initial step in moving from DNA databases to a comprehensive understanding of human biology. As a result of the explosion in nucleic acid sequence information and the concurrent development of methods for high-throughput functional characterization of gene products, the genomic revolution also promises to provide a new paradigm for drug discovery, enabling the identification of molecular drug targets in a significant number of human diseases. This molecular view of diseases has contributed to the importance of combining primary sequence data with three-dimensional structure and has increased the awareness of computational homology modeling and its potential to elucidate protein function. In particular, when important proteins or novel therapeutic targets are identified—like the family of protein tyrosine phosphatases (PTPs) (reviewed in reference 53)—a structure-function classification of such protein families becomes an invaluable framework for further advances in biomedical science. Here, we present a comparative analysis of the structural relationships among vertebrate PTP domains and provide a comprehensive resource for sequence analysis of phosphotyrosine-specific PTPs

Development of an evolutionary algorithm for crystal structure prediction

Die vorliegende Dissertation befasst sich mit der theoretischen Vorhersage neuer Materialien. Ein evolutionärer Algorithmus, der zur Lösung dieses globalen Optimierungsproblems Konzepte der natürlichen Evolution imitiert, wurde entwickelt und ist als Programmpaket EVO frei verfügbar. EVO findet zuverlässig sowohl bekannte als auch neuartige Kristallstrukturen. Beispielsweise wurden die Strukturen von Germaniumnitrofluorid, einer neue Borschicht und mit dem gekreuzten Graphen einer bisher unbekannte Kohlenstoffstruktur gefunden. Ferner wurde in der Arbeit gezeigt, dass das reine Auffinden solcher Strukturen der erste Teil einer erfolgreichen Vorhersage ist. Weitere aufwendige Berechnungen sind nötig, die Aufschluss über die Stabilität der hypothetischen Struktur geben und Aussagen über zu erwartende Materialeigenschaften liefern

Structure and mechanism of protein tyrosine phosphatase-like phytases

xix, 148 leaves : ill. (some col.) ; 29 cmThe structure and mechanism of the Protein Tyrosine Phosphatase-like Phytases (PTPLPs) from Selenomonas ruminantium (PhyAsr) and Mitsuokella multacida (PhyAmm) were investigated using a combination of enzyme kinetics, site-directed mutagenesis, and X-ray crystallography. I show that PTPLPs use a classical protein tyrosine phosphatase catalytic mechanism and adopt a core PTP fold. Several unique structural features of PTPLPs confer specificity for inositol phosphates. The effect of ionic strength and oxidation on the kinetics and structure of PTPLPs was investigated. The structural consequences of reversible and irreversible oxidation on PTPLPs and PTPs are compared and discussed. We determine the structural basis of substrate specificity in PTPLPs and propose a novel reaction mechanism for the hydrolysis of inositol polyphosphates by PTPLPs. Finally, the structure and function of a unique tandemly repeated phytase has been determined. We show that the active sites of the tandem repeat possess significantly different specificities for inositol polyphosphate

Bringing the Frame Into Focus: How Cable News Pundits Protect the Glass Ceiling

In many nations, the 21st century has been about women in politics. Not only are they running for prominent political offices, but they are winning them. The trend toward success for American female politicians has been slower to progress, however, as no women have been elected to the U.S. Presidency to date, and social science research suggests persistent gender biases exist in their news coverage. In order to explore the potential role that media play in continuing this gender disparity in U.S. politics, this comparative study investigates how cable pundit programs – a dramatic, partisan genre of “news” that has risen in popularity since the 2008 election – frame female candidates for the highest national office. A content analysis of pre-election coverage of three prominent U.S. politicians on the national scene, Hillary Clinton, Sarah Palin and Michele Bachmann, on The O’Reilly Factor, On the Record with Greta Van Susteren, The Last Word with Lawrence O’Donnell, Countdown with Keith Olbermann and The Rachel Maddow Show reveals a small incidence of gendered coverage across these shows overall. Among said coverage found, however, trends in the data suggest that conservative programs employ more gendered frames than liberal programs, and that those frames are particularly negative when referring to liberal candidates (Clinton), and positive when referring to conservative (Palin and Bachmann) candidates. Further, the gender of the pundits, the gender of the cable network production staff members, and the political party affiliations of executive staff/owners correspond to the frames employed by these programs in unique ways