다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Signaling Recognition Events with Fluorescent Sensors and Switches.

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Arsenic round the world: a review.

Atomically precise pieces of matter of nanometer dimensions composed of noble metals are new categories of materials with many unusual properties. Over 100 molecules of this kind with formulas such as Au25(SR)18, Au38(SR)24, and Au102(SR)44 as well as Ag25(SR)18, Ag29(S2R)12, and Ag44(SR)30 (often with a few counterions to compensate charges) are known now. They can be made reproducibly with robust synthetic protocols, resulting in colored solutions, yielding powders or diffractable crystals. They are distinctly different from nanoparticles in their spectroscopic properties such as optical absorption and emission, showing well-defined features, just like molecules. They show isotopically resolved molecular ion peaks in mass spectra and provide diverse information when examined through multiple instrumental methods. Most important of these properties is luminescence, often in the visible–near-infrared window, useful in biological applications. Luminescence in the visible region, especially by clusters prot...

Atomically Precise Clusters of Noble Metals: Emerging Link between Atoms and Nanoparticles

Phosphorylation is a key post-translational modification that alters the functional state of many proteins. The Escherichia coli toxin HipA, which phosphorylates glutamyl-tRNA synthetase and triggers bacterial persistence under stress, becomes inactivated upon autophosphorylation of Ser150. Interestingly, Ser150 is phosphorylation-incompetent in the crystal structure of HipA since it is deeply buried ("in-state"), although in the phosphorylated state it is solvent exposed ("out-state"). To be phosphorylated, a minor population of HipA must exist in the phosphorylation-competent "out-state" (solvent-exposed Ser150), not detected in the crystal structure of unphosphorylated HipA. Here we report a molten-globule-like intermediate of HipA at low urea (∼4 kcal/mol unstable than natively folded HipA). The intermediate is aggregation-prone, consistent with a solvent exposed Ser150 and its two flanking hydrophobic neighbors (Val/Ile) in the "out-state". Molecular dynamics simulations showed the HipA "in-out" pathway to contain multiple free energy minima with an increasing degree of Ser150 solvent exposure with the free energy difference between the "in-state" and the metastable exposed state(s) to be ∼2-2.5 kcal/mol, with unique sets of hydrogen bonds and salt bridges associated with the metastable loop conformations. Together, the data clearly identify the existence of a phosphorylation-competent metastable state of HipA. Our results not only suggest a mechanism of HipA autophosphorylation but also add to a number of recent reports on unrelated protein systems where the common proposed mechanism for phosphorylation of buried residues is their transient exposure even without phosphorylation.

Phosphorylation-Competent Metastable State of Escherichia coli Toxin HipA.

Norcryptotackieine (1a) belongs to the indoloquinoline class of alkaloids isolated from Cryptolepis sanguinolenta, a plant species that has been traditionally used as an antimalarial agent. Additional structural modifications of 1a can potentially enhance its therapeutic potency. Indoloquinolines such as cryptolepine, neocryptolepine, isocryptolepine, and neoisocryptolepine show restricted clinical applications owing to their cytotoxicity deriving from interactions with DNA. Here, we examined the effect of substitutions at the N-6 position of norcryptotackieine on the cytotoxicity, as well as structure-activity relationship studies pertaining to sequence specific DNA-binding affinities. The representative compound 6d binds DNA in a nonintercalative/pseudointercalative fashion, in addition to nonspecific stacking on DNA, in a sequence selective manner. The DNA-binding studies clearly establish the mechanism of DNA binding by N-6-substituted norcryptotackieines and neocryptolepine. The synthesized norcryptotackieines 6c,d and known indoloquinolines were screened on different cell lines (HEK293, OVCAR3, SKOV3, B16F10, and HeLa) to assess their cytotoxicity. Norcryptotackieine 6d (IC50 value of 3.1 μM) showed 2-fold less potency when compared to the natural indoloquinoline cryptolepine 1c (IC50 value of 1.64 μM) in OVCAR3 (ovarian adenocarcinoma) cell lines.

Sequence-Specific Dual DNA Binding Modes and Cytotoxicities of N-6-Functionalized Norcryptotackieine Alkaloids.

The canonical function of glutamyl-tRNA synthetase (GluRS) is to glutamylate tRNA Glu. Yet, not all bacterial GluRSs glutamylate tRNA Glu; many glutamylate both tRNA Glu and tRNA Gln, while some glutamylate only tRNA Gln and not the cognate substrate tRNA Glu. Understanding the basis of this unique tRNA Glx-specificity is important. Mutational studies have hinted at hotspot residues, both on tRNA Glx and GluRS, that play crucial roles in tRNA Glx-specificity. But the underlying structural basis remains unexplored. Majority of biochemical studies related to tRNA Glx-specificity have been performed on GluRS from Escherichia coli and other proteobacterial species. However, since the early crystal structures of GluRS and tRNA Glu-bound GluRS were from non-proteobacterial species ( Thermus thermophilus), the proteobacterial biochemical data have often been interpreted in the context of non-proteobacterial GluRS structures. Marked differences between proteoand non-proteobacterial GluRSs have been demonstrated and therefore it is important that tRNA Glx-specificity be understood vis-a-vis proteobacterial GluRS structures. Towards this goal we have solved the crystal structure of GluRS from E. coli. Using the solved structure and several other currently available proteoand non-proteobacterial GluRS crystal structures, we have probed the structural basis of tRNA Glx-specificity of bacterial GluRSs. Specifically, our analysis suggests a unique role played by a tRNA Glx D-helix contacting loop of GluRS in modulation of tRNA Gln-specificity. While earlier studies had identified functional hotspots on tRNA Glx that controlled tRNA Glx-specificity of GluRS, this is the first report of complementary signatures of tRNA Glx-specificity in GluRS. Signatures of tRNAGlx-specificity in bacterial glutamyl-tRNA synthetases Saumya Dasgupta,#1 Aditya Dev,#Nipa Chongdar,#2 Gautam Basu* Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata 700054, India. # Equal contribution. * Corresponding author (gautamda@gmail.com; gautam@jcbose.ac.in) 1. Current Address: Department of Chemistry, Amity Institute of Applied Sciences, Amity University Kolkata, WB 700135, India 2. Current Address: Interdisciplinary School of Life Sciences, Indian Institute of Technology, Goa, Farmagudi, Goa 403401, India. Email: nipa@iitgoa.ac.in

Gautam Basu

Papers

Phosphorylation-Competent Metastable State of Escherichia coli Toxin HipA.

Sequence-Specific Dual DNA Binding Modes and Cytotoxicities of N-6-Functionalized Norcryptotackieine Alkaloids.

Signatures of tRNA Glx -specificity in bacterial glutamyl-tRNA synthetases