Search

Research background: The aim of the scientific contribution is to analyze the aspect of Transport Development of the Greater Tumen Initiative. Economic cooperation among the countries of the Greater Tumen Initiative (GTI) is the basis for interaction in various fields, especially transport. Purpose of the article: However, taking into account the prevailing trends in Europe-Asia transportation, it is not entirely correct to make the implementation of GTI transport projects dependent on prospective transit freight flows. At first, it is necessary to concentrate on the transport support of foreign trade flows directly between the GTI member countries. Methods: We propose to assess the stability of foreign trade flows as a cargo base (current and potential) of transport projects within the GTI by absolute time series, which reflects the trend (or its absence, i.e. each next level is higher or lower than the previous one) and its stability, as well as by relative time series, i.e. growth rates, which reflects the stability of the change rate (the growth rate of each subsequent period is higher or lower than the previous one). Findings & Value added: Based on the results of the assessment of foreign trade flows between the member countries, that forms the current and potential cargo base of transport projects, it was concluded not only about a high degree of stability and potential of foreign economic cooperation, but also about the need of extra measures for its further intensifying, including foreign trade transport services improvement.

Aminoglycoside-2'-phosphotransferase-IIa [APH(2')-IIa] is one of a number of homologous bacterial enzymes responsible for the deactivation of the aminoglycoside family of antibiotics and is thus a major component in bacterial resistance to these compounds. APH(2')-IIa produces resistance to several clinically important aminoglycosides (including kanamycin and gentamicin) in both gram-positive and gram-negative bacteria, most notably in Enterococcus species. We have determined the structures of two complexes of APH(2')-IIa, the binary gentamicin complex and a ternary complex containing adenosine-5'-([beta],[gamma]-methylene) triphosphate (AMPPCP) and streptomycin. This is the first crystal structure of a member of the APH(2') family of aminoglycoside phosphotransferases. The structure of the gentamicin-APH(2')-IIa complex was solved by multiwavelength anomalous diffraction methods from a single selenomethionine-substituted crystal and was refined to a crystallographic R factor of 0.210 ([R.sub.free], 0.271) at a resolution of 2.5 [Angstrom]. The structure of the AMPPCP-streptomycin complex was solved by molecular replacement using the gentamicin-APH(2')-IIa complex as the starting model. The enzyme has a two-domain structure with the substrate binding site located in a cleft in the C-terminal domain. Gentamicin binding is facilitated by a number of conserved acidic residues lining the binding cleft, with the A and B rings of the substrate forming the majority of the interactions. The inhibitor streptomycin, although binding in the same pocket as gentamicin, is orientated such that no potential phosphorylation sites are adjacent to the catalytic aspartate residue. The binding of gentamicin and streptomycin provides structural insights into the substrate selectivity of the APH(2') subfamily of aminoglycoside phosphotransferases, specifically, the selectivity between the 4,6-disubstituted and the 4,5-disubstituted aminoglycosides.

Aminoglycoside 2'-Ib phosphotransferase [APH(2')-Ib] produces resistance to several clinically important aminoglycosides in Gram-positive and Gram-negative bacteria. Nuclear magnetic resonance analysis of the product of kanamycin A phosphorylation revealed that modification occurs at the 2'-hydroxyl of the aminoglycoside.

A study presents the characterization of the newly discovered aminoglycoside-modifying enzyme ANT(3'')-Ii/AAc(6')-IId from Serratia marcescens, which helps in the catalysis of adenylation and acetylation of aminoglycoside antibiotics. The analysis reveals that the adenyltransferase domain is highly specific to streptomycin and spectinomycin, whereas the acetyltransferase domain has a broad substrate profile.

The properties of inhibitor-resistant beta-lactamases, namely the clinically identified M69L mutant variant of the TEM-1 beta-lactamase from escherichia coli is described. The effects of the mutation on the behavior of the beta-lactamase were subtle, including the differences in the measured dissociation constants that account for the inhibitor-resistant trait.

Ribozymes are shown to catalyze the stereoselective formation of carbon-carbon between small organic molecules. The interactions of these Diels-Alderase ribozymes with their substrates and products are elucidated by chemical substitution analysis by using 44 different, varied analogues. The results highlight the intricacy of ribozyme active sites, which can control chemical reaction pathways based on minute differences in substrate stereochemistry and substitution pattern.

The structure of neamine bound to the A site of the bacterial ribosomal RNA is used in the design of novel aminoglycosides. A total of seven compounds are designed and subsequently synthesized, with the expectation that they would bind to the A-site RNA. All synthetic compounds are found to bind to the target RNA comparably to the present antibiotic neamine, with dissociation constants in the lower micromolar range.

[beta]-Lactamases are the resistance enzymes for [beta]-lactam antibiotics, of which four classes are known. [beta]-lactamases hydrolyze the [beta]-lactam moieties of these antibiotics, rendering them inactive. It is shown herein that the class D OXA-10 [beta]-lactamase depends critically on an unusual carbamylated lysine as the basic residue for both the enzyme acylation and deacylation steps of catalysis. The formation of carbamylated lysine is reversible. Evidence is presented that this enzyme is dimeric and carbamylated in living bacteria. High-resolution x-ray structures for the native enzyme were determined at pH values of 6.0, 6.5, 7.5, and 8.5. Two dimers are present per asymmetric unit. One monomer in each dimer was carbamylated at pH 6.0, whereas all four monomers were fully carbamylated at pH 8.5. At the intermediate pH values, one monomer of each dimer was carbamylated, and the other showed a mixture of carbamylated and non-carbamylated lysines. It would appear that, as the pH increased for the sample, additional lysines were 'titrated' by carbamylation. A handful of carbamylated lysines are known from protein crystallographic data, all of which have been attributed roles in structural stabilization (mostly as metal ligands) of the proteins. This paper reports a previously unrecognized role for a noncoordinated carbamylate lysine as a basic residue involved in mechanistic reactions of an enzyme, which indicates another means for expansion of the catalytic capabilities of the amino acids in nature beyond the 20 common amino acids in development of biological catalysts.

The kinetics of hydrolysis of cefepime, a novel cephalosporin, by the class A TEM(sub pUC19) beta-lactamase are examined. Conformational changes by the protein during enzymic hydrolysis of the lactam bond, which lead to the unraveling of the structure of the enzyme in a process not entirely revocable, are shown to be involved in the turnover of this molecule by the TEM(sub pUC19) beta-lactamase. It is shown further that hydrolysis of cefepime by this beta-lactamase involves a novel relaxation of the structure of the enzyme to accommodate the bulky C(sub 7beta) side chain of the antibiotic in the active site.