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1.067 Aktuelle Fachpublikationen von Proceedings of the National Academy of Sciences

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Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36 [Biochemistry]

02.02.2016 | Myles B. Poulin; Jessica L. Schneck; Rosalie E. Matico; Patrick J. McDevitt; Michael J. Huddleston; Wangfang Hou; Ne ..., Proceedings of the National Academy of Sciences current issue, 2016

Nuclear receptor SET domain containing protein 2 (NSD2) catalyzes the methylation of histone H3 lysine 36 (H3K36). It is a determinant in Wolf–Hirschhorn syndrome and is overexpressed in human multiple myeloma. Despite the relevance of NSD2 to cancer, there are no potent, selective inhibitors of ...

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Intrinsic regulation of FIC-domain AMP-transferases by oligomerization and automodification [Biochemistry]

02.02.2016 | Frédéric V. Stanger; Björn M. Burmann; Alexander Harms; Hugo Aragão; Adam Mazur; Timothy Sharpe; Christoph Dehio; Se ..., Proceedings of the National Academy of Sciences current issue, 2016

Filamentation induced by cyclic AMP (FIC)-domain enzymes catalyze adenylylation or other posttranslational modifications of target proteins to control their function. Recently, we have shown that Fic enzymes are autoinhibited by an α-helix (αinh) that partly obstructs the active site. For the ...

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Programmable polyproteams built using twin peptide superglues [Biochemistry]

02.02.2016 | Gianluca Veggiani; Tomohiko Nakamura; Michael D. Brenner; Raphaël V. Gayet; Jun Yan; Carol V. Robinson; Mark Howarth, Proceedings of the National Academy of Sciences current issue, 2016

Programmed connection of amino acids or nucleotides into chains introduced a revolution in control of biological function. Reacting proteins together is more complex because of the number of reactive groups and delicate stability. Here we achieved sequence-programmed irreversible connection of ...

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Constant molecular aging rates vs. the exponential acceleration of mortality [Biochemistry]

02.02.2016 | Caleb E. Finch; Eileen M. Crimmins, Proceedings of the National Academy of Sciences current issue, 2016

Laëtitia Gorisse, Philippe Gillery, and their coworkers (1) at the University of Reims elegantly document carbamylation as a biochemical change of aging in long-lived proteins that accumulates progressively across the life span. In human skin samples, the main carbamylation product, homocitruline ...

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Correction for Sohl et al., Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase {gamma} [Correction]

02.02.2016 | Proceedings of the National Academy of Sciences current issue, 2016

BIOCHEMISTRY Correction for “Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase γ,” by Christal D. Sohl, Michal R. Szymanski, Andrea C. Mislak, Christie K. Shumate, Sheida Amiralaei, Raymond F. Schinazi, Karen S. Anderson, and Y. Whitney ...

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Nicastrin guards Alzheimer’s gate [Biochemistry]

02.02.2016 | Siniša Urban, Proceedings of the National Academy of Sciences current issue, 2016

Alzheimer’s disease is characterized by protein deposits of amyloid-β as plaques in the brain (1). The suite of enzymes that produce amyloid-β by cutting it out of the amyloid-β precursor protein (APP) have long been considered to be prime targets for therapeutic intervention. Converting this ...

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Nicastrin functions to sterically hinder {gamma}-secretase-substrate interactions driven by substrate transmembrane domain [Biochemistry]

02.02.2016 | David M. Bolduc; Daniel R. Montagna; Yongli Gu; Dennis J. Selkoe; Michael S. Wolfe, Proceedings of the National Academy of Sciences current issue, 2016

γ-Secretase is an intramembrane-cleaving protease that processes many type-I integral membrane proteins within the lipid bilayer, an event preceded by shedding of most of the substrate’s ectodomain by α- or β-secretases. The mechanism by which γ-secretase selectively recognizes and recruits ...

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Structure of NDP-forming Acetyl-CoA synthetase ACD1 reveals a large rearrangement for phosphoryl transfer [Biochemistry]

02.02.2016 | Renato H.-J. Weiße; Annette Faust; Marcel Schmidt; Peter Schönheit; Axel J. Scheidig, Proceedings of the National Academy of Sciences current issue, 2016

The NDP-forming acyl-CoA synthetases (ACDs) catalyze the conversion of various CoA thioesters to the corresponding acids, conserving their chemical energy in form of ATP. The ACDs are the major energy-conserving enzymes in sugar and peptide fermentation of hyperthermophilic archaea. They are ...

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Discovery of RNA splicing and genes in pieces [Biochemistry]

26.01.2016 | Arnold J. Berk, Proceedings of the National Academy of Sciences current issue, 2016

The Problem: Short-Lived Heterogeneous Nuclear RNA During the 1960s and 1970s, there was a major conundrum in eukaryotic molecular biology regarding the synthesis of mRNA in animal cells. Pulse and pulse-chase radio-labeling experiments with tritiated uridine had shown that a large fraction of ...

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Intermediates in the assembly of mitotic checkpoint complexes and their role in the regulation of the anaphase-promoting complex [Biochemistry]

26.01.2016 | Sharon Kaisari; Danielle Sitry-Shevah; Shirly Miniowitz-Shemtov; Avram Hershko, Proceedings of the National Academy of Sciences current issue, 2016

The mitotic (or spindle assembly) checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. Kinetochores that are not attached properly to the mitotic spindle produce an inhibitory signal that prevents progression into ...

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