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789 Aktuelle Fachpublikationen von Proceedings of the National Academy of Sciences

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Label-free electrochemical detection of human methyltransferase from tumors [Biochemistry]

21.10.2014 | Ariel L. Furst; Natalie B. Muren; Michael G. Hill; Jacqueline K. Barton, Proceedings of the National Academy of Sciences current issue, 2014

The role of abnormal DNA methyltransferase activity in the development and progression of cancer is an essential and rapidly growing area of research, both for improved diagnosis and treatment. However, current technologies for the assessment of methyltransferase activity, particularly from crude ...

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The signaling phospholipid PIP3 creates a new interaction surface on the nuclear receptor SF-1 [Biochemistry]

21.10.2014 | Raymond D. Blind; Elena P. Sablin; Kristopher M. Kuchenbecker; Hsiu-Ju Chiu; Ashley M. Deacon; Debanu Das; Robert J. ..., Proceedings of the National Academy of Sciences current issue, 2014

The signaling phosphatidylinositol lipids PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3) bind nuclear receptor 5A family (NR5As), but their regulatory mechanisms remain unknown. Here, the crystal structures of human NR5A1 (steroidogenic factor-1, SF-1) ligand binding domain (LBD) bound to PIP2 and PIP3 ...

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Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death [Biochemistry]

21.10.2014 | Joanne M. Hildebrand; Maria C. Tanzer; Isabelle S. Lucet; Samuel N. Young; Sukhdeep K. Spall; Pooja Sharma; Catia Pi ..., Proceedings of the National Academy of Sciences current issue, 2014

Necroptosis is considered to be complementary to the classical caspase-dependent programmed cell death pathway, apoptosis. The pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) is an essential effector protein in the necroptotic cell death pathway downstream of the protein kinase Receptor ...

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Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation [Biochemistry]

21.10.2014 | Yaoyao Fu; Youngran Kim; Kyeong Sik Jin; Hyun Sook Kim; Jong Hyun Kim; DongMing Wang; Minyoung Park; Chang Hwa Jo; N ..., Proceedings of the National Academy of Sciences current issue, 2014

In higher eukaryotes, one of the two arginyl-tRNA synthetases (ArgRSs) has evolved to have an extended N-terminal domain that plays a crucial role in protein synthesis and cell growth and in integration into the multisynthetase complex (MSC). Here, we report a crystal structure of the MSC ...

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Structural basis of cellular dNTP regulation by SAMHD1 [Biochemistry]

14.10.2014 | Xiaoyun Ji; Chenxiang Tang; Qi Zhao; Wei Wang; Yong Xiong, Proceedings of the National Academy of Sciences current issue, 2014

The sterile alpha motif and HD domain-containing protein 1 (SAMHD1), a dNTPase, prevents the infection of nondividing cells by retroviruses, including HIV, by depleting the cellular dNTP pool available for viral reverse transcription. SAMHD1 is a major regulator of cellular dNTP levels in ...

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Basis for substrate recognition and distinction by matrix metalloproteinases [Biochemistry]

07.10.2014 | Boris I. Ratnikov; Piotr Cieplak; Kosi Gramatikoff; James Pierce; Alexey Eroshkin; Yoshinobu Igarashi; Marat Kazanov ..., Proceedings of the National Academy of Sciences current issue, 2014

Genomic sequencing and structural genomics produced a vast amount of sequence and structural data, creating an opportunity for structure–function analysis in silico [Radivojac P, et al. (2013) Nat Methods 10(3):221–227]. Unfortunately, only a few large experimental datasets exist to serve as ...

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Single-molecule investigation of G-quadruplex folds of the human telomere sequence in a protein nanocavity [Biochemistry]

07.10.2014 | Na An; Aaron M. Fleming; Eric G. Middleton; Cynthia J. Burrows, Proceedings of the National Academy of Sciences current issue, 2014

Human telomeric DNA consists of tandem repeats of the sequence 5′-TTAGGG-3′ that can fold into various G-quadruplexes, including the hybrid, basket, and propeller folds. In this report, we demonstrate use of the α-hemolysin ion channel to analyze these subtle topological changes at a nanometer ...

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Ribosome-induced tuning of GTP hydrolysis by a translational GTPase [Biochemistry]

07.10.2014 | Cristina Maracci; Frank Peske; Ev Dannies; Corinna Pohl; Marina V. Rodnina, Proceedings of the National Academy of Sciences current issue, 2014

GTP hydrolysis by elongation factor Tu (EF-Tu), a translational GTPase that delivers aminoacyl-tRNAs to the ribosome, plays a crucial role in decoding and translational fidelity. The basic reaction mechanism and the way the ribosome contributes to catalysis are a matter of debate. Here we use ...

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Pharmacologic rescue of an enzyme-trafficking defect in primary hyperoxaluria 1 [Biochemistry]

07.10.2014 | Non Miyata; Janos Steffen; Meghan E. Johnson; Sonia Fargue; Christopher J. Danpure; Carla M. Koehler, Proceedings of the National Academy of Sciences current issue, 2014

Primary hyperoxaluria 1 (PH1; Online Mendelian Inheritance in Man no. 259900), a typically lethal biochemical disorder, may be caused by the AGTP11LG170R allele in which the alanine:glyoxylate aminotransferase (AGT) enzyme is mistargeted from peroxisomes to mitochondria. AGT contains a C-terminal ...

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Molecular mechanics of 30S subunit head rotation [Biochemistry]

16.09.2014 | Srividya Mohan; John Paul Donohue; Harry F. Noller, Proceedings of the National Academy of Sciences current issue, 2014

During ribosomal translocation, a process central to the elongation phase of protein synthesis, movement of mRNA and tRNAs requires large-scale rotation of the head domain of the small (30S) subunit of the ribosome. It has generally been accepted that the head rotates by pivoting around the neck ...

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