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980 Aktuelle Fachpublikationen von Proceedings of the National Academy of Sciences

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Creative template-dependent synthesis by human polymerase mu [Biochemistry]

18.08.2015 | Andrea F. Moon; Rajendrakumar A. Gosavi; Thomas A. Kunkel; Lars C. Pedersen; Katarzyna Bebenek, Proceedings of the National Academy of Sciences current issue, 2015

Among the many proteins used to repair DNA double-strand breaks by nonhomologous end joining (NHEJ) are two related family X DNA polymerases, Pol λ and Pol µ. Which of these two polymerases is preferentially used for filling DNA gaps during NHEJ partly depends on sequence complementarity at the ...

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Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis [Biochemistry]

18.08.2015 | Daniel R. Marous; Evan P. Lloyd; Andrew R. Buller; Kristos A. Moshos; Tyler L. Grove; Anthony J. Blaszczyk; Squire J ..., Proceedings of the National Academy of Sciences current issue, 2015

Despite their broad anti-infective utility, the biosynthesis of the paradigm carbapenem antibiotic, thienamycin, remains largely unknown. Apart from the first two steps shared with a simple carbapenem, the pathway sharply diverges to the more structurally complex members of this class of β-lactam ...

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SufB intein of Mycobacterium tuberculosis as a sensor for oxidative and nitrosative stresses [Biochemistry]

18.08.2015 | Natalya I. Topilina; Cathleen M. Green; Pradeepa Jayachandran; Danielle S. Kelley; Matthew J. Stanger; Carol Lyn Pia ..., Proceedings of the National Academy of Sciences current issue, 2015

Inteins are mobile genetic elements that self-splice at the protein level. Mycobacteria have inteins inserted into several important genes, including those corresponding to the iron-sulfur cluster assembly protein SufB. Curiously, the SufB inteins are found primarily in mycobacterial species that ...

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C-S bond cleavage by a polyketide synthase domain [Biochemistry]

18.08.2015 | Ming Ma; Jeremy R. Lohman; Tao Liu; Ben Shen, Proceedings of the National Academy of Sciences current issue, 2015

Leinamycin (LNM) is a sulfur-containing antitumor antibiotic featuring an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety is essential for LNM’s antitumor activity, by virtue of its ability to ...

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Essential role for polymerase specialization in cellular nonhomologous end joining [Biochemistry]

18.08.2015 | John M. Pryor; Crystal A. Waters; Ana Aza; Kenjiro Asagoshi; Christina Strom; Piotr A. Mieczkowski; Luis Blanco; Dal ..., Proceedings of the National Academy of Sciences current issue, 2015

Nonhomologous end joining (NHEJ) repairs chromosome breaks and must remain effective in the face of extensive diversity in broken end structures. We show here that this flexibility is often reliant on the ability to direct DNA synthesis across strand breaks, and that polymerase (Pol) μ and Pol λ ...

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Divergent evolution of an atypical S-adenosyl-l-methionine-dependent monooxygenase involved in anthracycline biosynthesis [Biochemistry]

11.08.2015 | Thadée Grocholski; Pedro Dinis; Laila Niiranen; Jarmo Niemi; Mikko Metsä-Ketelä, Proceedings of the National Academy of Sciences current issue, 2015

Bacterial secondary metabolic pathways are responsible for the biosynthesis of thousands of bioactive natural products. Many enzymes residing in these pathways have evolved to catalyze unusual chemical transformations, which is facilitated by an evolutionary pressure promoting chemical diversity. ...

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Inactive conformation enhances binding function in physiological conditions [Biochemistry]

11.08.2015 | Olga Yakovenko; Veronika Tchesnokova; Evgeni V. Sokurenko; Wendy E. Thomas, Proceedings of the National Academy of Sciences current issue, 2015

Many receptors display conformational flexibility, in which the binding pocket has an open inactive conformation in the absence of ligand and a tight active conformation when bound to ligand. Here we study the bacterial adhesin FimH to address the role of the inactive conformation of the pocket ...

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SOD1 aggregation in ALS mice shows simplistic test tube behavior [Biochemistry]

11.08.2015 | Lisa Lang; Per Zetterström; Thomas Brännström; Stefan L. Marklund; Jens Danielsson; Mikael Oliveberg, Proceedings of the National Academy of Sciences current issue, 2015

A longstanding challenge in studies of neurodegenerative disease has been that the pathologic protein aggregates in live tissue are not amenable to structural and kinetic analysis by conventional methods. The situation is put in focus by the current progress in demarcating protein aggregation in ...

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Two transcription pause elements underlie a {sigma}70-dependent pause cycle [Biochemistry]

11.08.2015 | Eric J. Strobel; Jeffrey W. Roberts, Proceedings of the National Academy of Sciences current issue, 2015

The movement of RNA polymerase (RNAP) during transcription elongation is modulated by DNA-encoded elements that cause the elongation complex to pause. One of the best-characterized pause sequences is a binding site for the σ70 initiation factor that induces pausing at a site near lambdoid phage ...

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Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination [Biochemistry]

11.08.2015 | Franziska Mortensen; Daniel Schneider; Tanja Barbic; Anna Sladewska-Marquardt; Simone Kühnle; Andreas Marx; Martin S ..., Proceedings of the National Academy of Sciences current issue, 2015

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss ...

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