Journal Articles

Large Exciton Energy Shifts by Reversible Surface Exchange in 2D II–VI Nanocrystals

Journal of American Chemical Society - Wed, 11/25/2015 - 15:48

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b09343
Categories: Journal Articles

Conjugation between σ- and π-Aromaticity in 1-C-Arylated Monocarba-closo-dodecaborate Anions

Journal of American Chemical Society - Wed, 11/25/2015 - 14:23

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b10321
Categories: Journal Articles

Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages: Investigation of “Shapeshifting” Properties

Journal of American Chemical Society - Wed, 11/25/2015 - 13:23

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b09825
Categories: Journal Articles

Issue Information

Protein Science - Wed, 11/25/2015 - 10:16
Categories: Journal Articles

In This Issue

Protein Science - Wed, 11/25/2015 - 10:16
Categories: Journal Articles

Mechanistic Insights into the H2S-Mediated Reduction of Aryl Azides Commonly Used in H2S Detection

Journal of American Chemical Society - Wed, 11/25/2015 - 08:04

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b10675
Categories: Journal Articles

Tumor Acidity-Sensitive Polymeric Vector for Active Targeted siRNA Delivery

Journal of American Chemical Society - Wed, 11/25/2015 - 08:01

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b09602
Categories: Journal Articles

Reads2Type: a web application for rapid microbial taxonomy identification

BMC Bioinformatics - Wed, 11/25/2015 - 07:00
Background: Identification of bacteria may be based on sequencing and molecular analysis of a specific locus such as 16S rRNA, or a set of loci such as in multilocus sequence typing. In the near future, healthcare institutions and routine diagnostic microbiology laboratories may need to sequence the entire genome of microbial isolates. Therefore we have developed Reads2Type, a web-based tool for taxonomy identification based on whole bacterial genome sequence data. Results: Raw sequencing data provided by the user are mapped against a set of marker probes that are derived from currently available bacteria complete genomes. Using a dataset of 1003 whole genome sequenced bacteria from various sequencing platforms, Reads2Type was able to identify the species with 99.5 % accuracy and on the minutes time scale. Conclusions: In comparison with other tools, Reads2Type offers the advantage of not needing to transfer sequencing files, as the entire computational analysis is done on the computer of whom utilizes the web application. This also prevents data privacy issues to arise. The Reads2Type tool is available at http://www.cbs.dtu.dk/~dhany/reads2type.html.
Categories: Journal Articles

Outer domains of integrase within retroviral intasomes are dispensible for catalysis of DNA integration

Protein Science - Wed, 11/25/2015 - 02:56
Abstract

Retroviral DNA integration is mediated by nucleoprotein complexes (intasomes) comprising a pair of viral DNA ends synapsed by a tetramer of integrase. Current integrase inhibitors act on intasomes rather than free integrase protein. Structural and functional studies of intasomes are essential to understand their mechanism of action and how the virus can escape by mutation. To date, prototype foamy virus (PFV) is the only retrovirus for which high-resolution structures of intasomes have been determined. In the PFV intasome structure, only the core domains of the outer subunits are ordered; the N-terminal domain, C-terminal domain, and N-terminal extension domain are disordered. Are these “missing domains” required for function or are they dispensable? We have devised a strategy to assemble “hetero-intasomes” in which the outer domains are not present as a tool to assess the functional role of the missing domains for catalysis of integration. We find that the disordered domains of outer subunits are not required for intasome assembly or catalytic activity as catalytic core domains can substitute for the outer subunits in the case of both PFV and HIV-1 intasomes.

Categories: Journal Articles

Effect of methylation on the side-chain pKa value of arginine

Protein Science - Wed, 11/25/2015 - 02:56
Abstract

Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 ± 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition.

Categories: Journal Articles

Structural investigations of the p53/p73 homologs from the tunicate species Ciona intestinalis reveal the sequence requirements for the formation of a tetramerization domain

Protein Science - Wed, 11/25/2015 - 00:10
Abstract

Most members of the p53 family of transcription factors form tetramers. Responsible for determining the oligomeric state is a short oligomerization domain consisting of one β-strand and one α-helix. With the exception of human p53 all other family members investigated so far contain a second α-helix as part of their tetramerization domain. Here we have used nuclear magnetic resonance spectroscopy to characterize the oligomerization domains of the two p53-like proteins from the tunicate Ciona intestinalis, representing the closest living relative of vertebrates. Structure determination reveals for one of the two proteins a new type of packing of this second α-helix on the core domain that was not predicted based on the sequence, while the other protein does not form a second helix despite the presence of crucial residues that are conserved in all other family members that form a second helix. By mutational analysis, we identify a proline as well as large hydrophobic residues in the hinge region between both helices as the crucial determinant for the formation of a second helix.

Categories: Journal Articles

Single fluorescence probes along the reactive center loop reveal site-specific changes during the latency transition of PAI-1

Protein Science - Wed, 11/25/2015 - 00:10
Abstract

The serine protease inhibitor (serpin), plasminogen activator inhibitor-1 (PAI-1), is an important biomarker for cardiovascular disease and many cancers. It is therefore a desirable target for pharmaceutical intervention. However, to date, no PAI-1 inhibitor has successfully reached clinical trial, indicating the necessity to learn more about the mechanics of the serpin. Although its kinetics of inhibition have been extensively studied, less is known about the latency transition of PAI-1, in which the solvent-exposed reactive center loop (RCL) inserts into its central β-sheet, rendering the inhibitor inactive. This spontaneous transition is concomitant with a large translocation of the RCL, but no change in covalent structure. Here, we conjugated the fluorescent probe, NBD, to single positions along the RCL (P13-P5′) to detect changes in solvent exposure that occur during the latency transition. The results support a mousetrap-like RCL-insertion that occurs with a half-life of 1–2 h in accordance with previous reports. Importantly, this study exposes unique transitions during latency that occur with a half-life of ∼5 and 25 min at the P5′ and P8 RCL positions, respectively. We hypothesize that the process detected at P5′ represents s1C detachment, while that at P8 results from a steric barrier to RCL insertion. Together, these findings provide new insights by characterizing multiple steps in the latency transition.

Categories: Journal Articles

Evidence for an essential role of intradimer interaction in catalytic function of carnosine dipeptidase II using electrospray-ionization mass spectrometry

Protein Science - Wed, 11/25/2015 - 00:10
Abstract

Carnosine dipeptidase II (CN2/CNDP2) is an M20 family metallopeptidase that hydrolyses various dipeptides including β-alanyl-l-histidine (carnosine). Crystallographic analysis showed that CN2 monomer is composed of one catalytic and one dimerization domains, and likely to form homodimer. In this crystal, H228 residue of the dimerization domain interacts with the substrate analogue bestatin on the active site of the dimer counterpart, indicating that H228 is involved in enzymatic reaction. In the present study, the role of intradimer interaction of CN2 in its catalytic activity was investigated using electrospray-ionization time-of-flight mass spectrometry (ESI-TOF MS). First, a dimer interface mutant I319K was prepared and shown to be present as a folded monomer in solution as examined by using ESI-TOF MS. Since the mutant was inactive, it was suggested that dimer formation is essential to its enzymatic activity. Next, we prepared H228A and D132A mutant proteins with different N-terminal extended sequences, which enabled us to monitor dimer exchange reaction by ESI-TOF MS. The D132A mutant is a metal ligand mutant and also inactive. But the activity was partially recovered time-dependently when H228A and D132A mutant proteins were incubated together. In parallel, H228A/D132A heterodimer was formed as detected by ESI-TOF MS, indicating that interaction of a catalytic center with H228 residue of the other subunit is essential to the enzymatic reaction. These results provide evidence showing that intradimer interaction of H228 with the reaction center of the dimer counterpart is essential to the enzymatic activity of CN2.

Categories: Journal Articles

The way forward is through Paris

Nature - Wed, 11/25/2015 - 00:00

The way forward is through Paris

Nature 527, 7579 (2015). doi:10.1038/527409a

Leaders must come together on a solid agreement at the United Nations climate conference — and then get to work at home by meeting commitments and finding new ways to reduce emissions.

Categories: Journal Articles

Built on trust

Nature - Wed, 11/25/2015 - 00:00

Built on trust

Nature 527, 7579 (2015). doi:10.1038/527410a

Written agreements between parties in research collaborations are not a sign of a lack of faith.

Categories: Journal Articles

A ‘perfect’ agreement in Paris is not essential

Nature - Wed, 11/25/2015 - 00:00

A ‘perfect’ agreement in Paris is not essential

Nature 527, 7579 (2015). http://www.nature.com/doifinder/10.1038/527411a

Author: Johan Rockström

Success at the latest climate talks will be a recognition by the world’s nations that incremental change will not do the job, says Johan Rockström.

Categories: Journal Articles
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