In experimental rabbits, cysteine injected intravenously in a dose of 1000 mg/kg temporarily bound zinc in β cells and prevented the formation of chelate zinc complexes in response to subsequent injection of diabetogenic zinc-binding substances that induce cell destruction. Injection of cysteine to animals was associated with a sharply negative reaction to zinc in β cells, which attests to blockade of zinc ions. Injection of cysteine few minutes after dithizone and formation of zinc-dithizone complex was followed by displacement of dithizone from the complex and prevented the development of diabetes in most animals. The most plausible mechanism of preventive effect of cysteine is the formation of 2:1 zinc-cysteine complex in β cells with possible fixation of Zn atom between sulfur atoms from SH groups of two cysteine molecules.
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http://dx.doi.org/10.1007/s10517-020-04765-1 | DOI Listing |
Structure
January 2025
RNAP Laboratory, Institute for Structural and Molecular Biology, University College London, London WC1E 6BT, UK. Electronic address:
N-utilization substance A (NusA) is a regulatory factor with pleiotropic functions in gene expression in bacteria. Archaea encode two conserved small proteins, NusA1 and NusA2, with domains orthologous to the two RNA binding K Homology (KH) domains of NusA. Here, we report the crystal structures of NusA2 from Sulfolobus acidocaldarius and Saccharolobus solfataricus obtained at 3.
View Article and Find Full Text PDFJ Chem Inf Model
February 2024
Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
The sulfonamide function is used extensively as a general building block in various inhibitory scaffolds and, more specifically, as a zinc-binding group (ZBG) of metalloenzyme inhibitors. Here, we provide biochemical, structural, and computational characterization of a metallopeptidase in complex with inhibitors, where the mono- and bisubstituted sulfamide functions are designed to directly engage zinc ions of a bimetallic enzyme site. Structural data showed that while monosubstituted sulfamides coordinate active-site zinc ions via the free negatively charged amino group in a canonical manner, their bisubstituted counterparts adopt an atypical binding pattern divergent from expected positioning of corresponding tetrahedral reaction intermediates.
View Article and Find Full Text PDFEur J Med Chem
January 2024
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Chinese Academy of Medical Sciences, Beijing, 100050, China. Electronic address:
Simultaneous inhibition of PI3K and HDAC has shown promise for treating various cancers, leading to discovery and development of their dual inhibitors as novel anticancer agents. Herein, we disclose a new series of PI3K/HDAC dual inhibitors bearing a benzamide moiety as the pharmacophore of HDAC inhibition. Based on systematic structure-activity relationship study, compounds 36 and 51 featuring an alkyl and benzoyl linker respectively were identified with favorable potencies against both PI3K and HDAC.
View Article and Find Full Text PDFExpert Opin Ther Pat
November 2023
Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France.
Introduction: Metallo-β-lactamases (MBLs) are enzymes produced by bacteria that confer resistance to most β-lactam antibiotics, including carbapenems, which have the broadest spectrum of activity. This resistance mechanism poses a significant threat to public health as it drastically reduces treatment options for severe bacterial infections. Developing effective inhibitors against MBLs is crucial to restore susceptibility to β-lactam antibiotics.
View Article and Find Full Text PDFProtein J
October 2023
State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and the Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, PR China.
Tryptic hydrolysates of protein fractions obtained by the Osborne method from chickpea (Cicer arietinum L.) seeds interacted with zinc ions and the results of chelation were monitored by the Energy Dispersive X-Ray (EDX) technique. The glutelin hydrolysate (GluHyd) reacted with zinc ions and depicted a relatively higher zinc content.
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