A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate

The biosynthesis of nitriles is known to occur through specialized pathways involving multiple enzymes; however, in bacterial and archeal biosynthesis of 7‐deazapurines, a single enzyme, ToyM, catalyzes the conversion of the carboxylic acid containing 7‐carboxy‐7‐deazaguanine (CDG) into its corresponding nitrile, 7‐cyano‐7‐deazaguanine (preQ₀). The mechanism of this unusual direct transformation was shown to proceed via the adenylation of CDG, which activates it to form the newly discovered amide intermediate 7‐amido‐7‐deazaguanine (ADG). This is subsequently dehydrated to form the nitrile in a process that consumes a second equivalent of ATP. The authentic amide intermediate is shown to be chemically and kinetically competent. The ability of ToyM to activate two different substrates, an acid and an amide, accounts for this unprecedented one‐enzyme catalysis of nitrile synthesis, and the differential rates of these two half reactions suggest that this catalytic ability is derived from an amide synthetase that gained a new function.     

Influence of ultrasound on nanostructural iron formed by electrochemical reduction

A method for control of particle dimensions of nanostructural amorphous iron powder obtained by electrochemical reduction under the effect of ultrasonic oscillations in reaction medium is described in this paper. Depending on the character of ultrasonic oscillations nanostructural powders were obtained differing both in average dimension and distribution of particle dimensions. In the case of simultaneous sonocation using ultrasonic vibrations with frequencies differing from each other by a factor of ten (20 and 200 kHz), the effect is complex, but includes narrowing of the average particle dimension.     

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

Molecular Diversity - A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All...     

Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin

Pyrrolopyrimidine nucleosides analogs, collectively referred to as deazapurines, are an important class of structurally diverse compounds found in a wide variety of biological niches. In this report, a cluster of genes from Streptomyces rimosus (ATCC 14673) involved in production of the deazapurine antibiotics sangivamycin and toyocamycin was identified. The cluster includes toyocamycin nitrile hydratase, an enzyme that catalyzes the conversion of toyocamycin to sangivamycin. In addition to this rare nitrile hydratase, the cluster encodes a GTP cyclohydrolase I, linking the biosynthesis of deazapurines to folate biosynthesis, and a set of purine salvage/biosynthesis genes, which presumably convert the guanine moiety from GTP to the adenine-like deazapurine base found in toyocamycin and sangivamycin. The gene cluster presented here could potentially serve as a model to allow identification of deazapurine biosynthetic pathways in other bacterial species.     

Improving the Graphical Lasso Estimation for the Precision Matrix Through Roots of the Sample Covariance Matrix

In this article, we focus on the estimation of a high-dimensional inverse covariance (i.e., precision) matrix. We propose a simple improvement of the graphical Lasso (glasso) framework that is able to attain better statistical performance without increasing significantly the computational cost. The proposed improvement is based on computing a root of the sample covariance matrix to reduce the spread of the associated eigenvalues. Through extensive numerical results, using both simulated and real datasets, we show that the proposed modification improves the glasso procedure. Our results reveal that the square-root improvement can be a reasonable choice in practice. Supplementary material for this article is available online.     

Reply to “A comment on “A test of general relativity using the LARES and LAGEOS satellites and a GRACE Earth gravity model,by I. Ciufolini et al.””

In 2016, we published “A test of general relativity using the LARES and LAGEOS satellites and a GRACE Earth’s gravity model. Measurement of Earth’s dragging of inertial frames [1]”, a measurement of frame-dragging, a fundamental prediction of Einstein’s theory of General Relativity, using the laser-ranged satellites LARES, LAGEOS and LAGEOS 2. The formal error, or precision, of our test was about 0.2% of frame-dragging, whereas the systematic error was estimated to be about 5%. In the 2017 paper “A comment on “A test of general relativity using the LARES and LAGEOS satellites and a GRACE Earth’s gravity model by I. Ciufolini et al.”” by L. Iorio [2] (called I2017 in the following), it was incorrectly claimed that, when comparing different Earth’s gravity field models, the systematic error in our test due to the Earth’s even zonal harmonics of degree 6, 8, 10 could be as large as 15%, 6% and 36%, respectively. Furthermore, I2017 contains other, also incorrect, claims about the number of necessary significant decimal digits of the coefficients used in our test (claimed to be nine), in order to eliminate the largest uncertainties in the even zonals of degree 2 and 4, and about the non-repeatability of our test. Here we analyze and rebut those claims in I2017.     

Cobalamin‐Dependent and Cobalamin‐Independent Methionine Synthases: Are There Two Solutions to the Same Chemical Problem?

Two enzymes in Escherichia coli, cobalamin‐independent methionine synthase (MetE) and cobalamin‐dependent methionine synthase (MetH), catalyze the conversion of homocysteine (Hcy) to methionine using N(5)‐methyltetrahydrofolate (CH₃‐H₄folate) as the Me donor. Despite the absence of sequence homology, these enzymes employ very similar catalytic strategies. In each case, the pK_a for the SH group of Hcy is lowered by coordination to Zn²⁺, which increases the concentration of the reactive thiolate at neutral pH. In each case, activation of CH₃‐H₄folate appears to involve protonation at N(5). CH₃‐H₄folate remains unprotonated in binary E?CH₃‐H₄folate complexes, and protonation occurs only in the ternary E?CH₃‐H₄folate?Hcy complex in MetE, or in the ternary E?CH₃‐H₄folate?cob(I)alamin complex in MetH. Surprisingly, the similarities are proposed to extend to the structures of these two unrelated enzymes. The structure of a homologue of the Hcy‐binding region of MetH, betaine? homocysteine methyltransferase, has been determined. A search of the three‐dimensional‐structure data base by means of the structure‐comparison program DALI indicates similarity of the BHMT structure with that of uroporphyrin decarboxylase (UroD), a homologue of the MT2‐A and MT2‐M proteins from Archaea, which catalyze Me transfers from methylcorrinoids to coenzyme M and share the Zn‐binding scaffold of MetE. Here, we present a model for the Zn binding site of MetE, obtained by grafting the Zn ligands of MT2‐A onto the structure of UroD.     

New ciprofloxacin–dithiocarbamate–benzyl hybrids: design,synthesis, antibacterial evaluation,and molecular modeling studies

Research on Chemical Intermediates - We designed and synthesized a series of new ciprofloxacin–dithiocarbamate–benzyl hybrids 5a–n as potential antibacterial agents. All of the...     

Dioldehydratase Binds Coenzyme B12 in the “Base-On” Mode: ESR Investigations on Cob(II)alamin

Even in the enzyme-bound state the dimethylbenzimidazole ligand in the dioldehydratase from Salmonella typhimurium remains bound to the cobalt ion in contrast to some coenzyme B₁₂-dependent enzymes. Direct, ESR spectroscopic proof for this “base-on” binding mode was obtained by using a coenzyme in which one of the nitrogen atoms of the dimethylbenzimidazole ligand was ¹⁵N labeled (see schematic representation on the right).