Saponins as cytotoxic agents: an update (2010–2021). Part II—Triterpene saponins

Phytochemistry Reviews - Saponins make up an important group of natural glycosidic compounds which are distinguished by triterpene or steroidal aglycone. Although widely distributed in terrestrial...     

Kinetics and mechanisms of the CO2 and SO2 uptake by coordinate ion, cis-[Cr(C2O4)(L-L)(OH2)2] {(L-L) = methyl 3-amino-2,3-dideoxy-α-d-arabino-hexopyranoside} as studied by stopped-flow spectrophotometry

The kinetics of CO₂ and SO₂ uptake by a coordinate ion, cis-[Cr(C₂O₄)(L-L)(OH₂)₂]⁺, where L-L stands for a bidentate sugar ligand, methyl 3-amino-2,3-dideoxy-α-d-arabino-hexopyranoside has been studied, over temperature ranges of 5 - 25 and 5 - 20 °C for CO₂ and SO₂, respectively. Investigations were carried out using stopped-flow spectrophotometry in the range of 340-700 nm. Results of the kinetic measurements obtained for both gases were compared. The kinetics and mechanisms of the reactions were suggested and ΔH^‡ values for both processes were determined.     

Crystal structure of methyl 3-amino-2,3-dideoxy-beta-D-arabino-hexopyranoside. Stabilization of the crystal lattice by a double network of N-H...O, O-H...N and O-H...O interactions

The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-beta-D-arabino-hexopyranoside were investigated by (1)H NMR, (13)C NMR and IR spectroscopy, as well as by optical rotation. The crystal structure was confirmed by single-crystal X-ray crystallographic analysis at 293 K and R = 0.0434 based on 910 independent reflections. The crystal belongs to the monoclinic system, space group of P2(1) with cell dimensions a = 6.050(1) Angstroms, b = 7.284(1) Angstroms, c = 10.289(2) Angstroms, beta = 104.69(3) degrees, D(c) = 1.341 Mg cm(-3) and V = 438.9(1) Angstroms(3) for Z = 2. Furthermore, the molecule has a typical (4)C(1) chair conformation. Hydrogen bonds between sugar molecules are responsible for stabilizing the crystal lattice.     

Molecular genetic analysis of the GJB1 gene: a study of six mutations

Charcot-Marie-Tooth type X1 disease (CMTX1) is an X-dominant peripheral neuropathy caused by mutations in the GJB1 gene. Molecular genetic analysis of the GJB1 gene is crucial for CMTX1 diagnosis and for genetic counselling. To date, molecular genetic analysis of the GJB1 gene revealed 264 mutations in the GJB1 gene. In spite of the rising number of GJB1 gene mutations, family history was documented in only a few CMTX1 cases. The aim of this study was a molecular genetic analysis of the GJB1 gene in 7 families, performed in 19 CMTX1-affected patients and 13 healthy family members. Moreover, we attempted to report evidence of effects of 6 amino-acid substitutions described in this study. To the best of our knowledge, the G110D, V152D and K167E mutations are novel substitutions, which have not been reported so far.     

DNA3′pp5′G de-capping activity of aprataxin: effect of cap nucleoside analogs and structural basis for guanosine recognition

DNA_3′pp_5′G caps synthesized by the 3′-PO₄/5′-OH ligase RtcB have a strong impact on enzymatic reactions at DNA 3′-OH ends. Aprataxin, an enzyme that repairs A_5′pp_5′DNA ends formed during abortive ligation by classic 3′-OH/5′-PO₄ ligases, is also a DNA 3′ de-capping enzyme, converting DNAppG to DNA_3′p and GMP. By taking advantage of RtcB''s ability to utilize certain GTP analogs to synthesize DNAppN caps, we show that aprataxin hydrolyzes inosine and 6-O-methylguanosine caps, but is not adept at removing a deoxyguanosine cap. We report a 1.5 Å crystal structure of aprataxin in a complex with GMP, which reveals that: (i) GMP binds at the same position and in the same anti nucleoside conformation as AMP; and (ii) aprataxin makes more extensive nucleobase contacts with guanine than with adenine, via a hydrogen bonding network to the guanine O6, N1, N2 base edge. Alanine mutations of catalytic residues His147 and His149 abolish DNAppG de-capping activity, suggesting that the 3′ de-guanylylation and 5′ de-adenylylation reactions follow the same pathway of nucleotidyl transfer through a covalent aprataxin-(His147)–NMP intermediate. Alanine mutation of Asp63, which coordinates the guanosine ribose hydroxyls, impairs DNAppG de-capping.     

Point Mutations in FimH Adhesin of Crohn's Disease-Associated Adherent-Invasive Escherichia coli Enhance Intestinal Inflammatory Response

Adherent-invasive Escherichia coli (AIEC) are abnormally predominant on Crohn''s disease (CD) ileal mucosa. AIEC reference strain LF82 adheres to ileal enterocytes via the common type 1 pili adhesin FimH and recognizes CEACAM6 receptors abnormally expressed on CD ileal epithelial cells. The fimH genes of 45 AIEC and 47 non-AIEC strains were sequenced. The phylogenetic tree based on fimH DNA sequences indicated that AIEC strains predominantly express FimH with amino acid mutations of a recent evolutionary origin - a typical signature of pathoadaptive changes of bacterial pathogens. Point mutations in FimH, some of a unique AIEC-associated nature, confer AIEC bacteria a significantly higher ability to adhere to CEACAM-expressing T84 intestinal epithelial cells. Moreover, in the LF82 strain, the replacement of fimH _LF82 (expressing FimH with an AIEC-associated mutation) with fimH _K12 (expressing FimH of commensal E. coli K12) decreased the ability of bacteria to persist and to induce severe colitis and gut inflammation in infected CEABAC10 transgenic mice expressing human CEACAM receptors. Our results highlight a mechanism of AIEC virulence evolution that involves selection of amino acid mutations in the common bacterial traits, such as FimH protein, and leads to the development of chronic inflammatory bowel disease (IBD) in a genetically susceptible host. The analysis of fimH SNPs may be a useful method to predict the potential virulence of E. coli isolated from IBD patients for diagnostic or epidemiological studies and to identify new strategies for therapeutic intervention to block the interaction between AIEC and gut mucosa in the early stages of IBD.