HypA, a nickel accessory protein from H. pylori, binds a zinc ion in it's structural site, a loop with two conserved CXXC motifs (Ac-ELECKDCSHVFKPNALDYGVCEKCHS-NH(2)). There are at least three hypotheses on the binding mode of this ion. In this paper, we try to understand how Zn(2+) binds to this fragment and why Ni(2+), a metal with quite a high affinity towards thiolic sites, doesn't compete with zinc in the binding to this motif. Potentiometric titrations, mass spectrometry, NMR, UV-Vis and CD spectroscopy help us to compare the coordination modes in both metal complexes and discuss their thermodynamic stabilities.
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http://dx.doi.org/10.1039/c2dt32195e | DOI Listing |
Arch Biochem Biophys
December 2024
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, 226017, India. Electronic address:
This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (HA3, 9F4, EBE, and TFG) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (HA3, 9F4, EBE) or diol (TFG) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation.
View Article and Find Full Text PDFSAR QSAR Environ Res
August 2024
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
MMP-2 overexpression is strongly related to several diseases including cancer. However, none of the MMP-2 inhibitors have been marketed as drug candidates due to various adverse effects. Here, a set of sulphonyl pyrrolidines was subjected to validation of molecular modelling followed by binding mode analysis to explore the crucial structural features required for the discovery of promising MMP-2 inhibitors.
View Article and Find Full Text PDFAnimals (Basel)
February 2024
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, College of Fisheries, Southwest University, Chongqing 402460, China.
Zygote arrest-1 (Zar1) and Wilms' tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, and were identified in Asian seabass (), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family.
View Article and Find Full Text PDFFoods
November 2023
Faculty of Health Sciences of Trairi, Federal University of Rio Grande do Norte (UFRN), Santa Cruz 59200000, Brazil.
The search for improvements in quality of life has increasingly involved changes in the diet, especially the consumption of foods which, in addition to having good nutritional value, are characterized by offering health benefits. Among the molecules that trigger several beneficial responses are peptides, which are specific fragments of proteins known to produce positive effects on the human body. This review aimed to discuss the bioactive potential of peptides from cheeses.
View Article and Find Full Text PDFEur J Med Chem
February 2024
Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan; The Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan. Electronic address:
Dual-targeting anticancer agents 4-29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction.
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