Role of metal–ligand coordination in the folding pathway of zinc finger peptides

A series of porphyrin triads (1–6), based on the reaction of trans-dihydroxo-[5,15-bis(3-pyridyl)-10,20-bis(phenyl)porphyrinato]tin(IV) (SnP) with six different phenoxy Zn(II)-porphyrins (ZnLn), was synthesized. The cooperative metal–ligand coordination of 3-pyridyl nitrogens in the SnP with the phenoxy Zn(II)-porphyrins, followed by the self-assembly process, leads to the formation of nanostructures. The red-shifts and remarkable broadening of the absorption bands in the UV–vis spectra for the triads in CHCl3 indicate that nanoaggregates may be produced in the self-assembly process of these triads. The emission intensities of the triads were also significantly reduced due to the aggregation. Microscopic analyses of the nanostructures of the triads reveal differences due to the different substituents on the axial Zn(II)-porphyrin moieties. All these nanomaterials exhibited efficient photocatalytic performances in the degradation of rhodamine B (RhB) dye under visible light irradiation, and the degradation efficiencies of RhB in aqueous solution were observed to be 72~95% within 4 h. In addition, the efficiency of the catalyst was not impaired, showing excellent recyclability even after being applied for the degradation of RhB in up to five cycles.

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Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽

10.3390/v13061092 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1092

Author(s):

János András Mótyán ◽

Márió Miczi ◽

Stephen Oroszlan ◽

József Tőzsér

Keyword(s):

Amino Acid ◽

Zinc Finger ◽

Cleavage Site ◽

Potential Role ◽

Binding Mode ◽

Interaction Energies ◽

Vitro Assay ◽

Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

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The Only Function of Grauzone Required for Drosophila Oocyte Meiosis Is Transcriptional Activation of the cortex Gene

Genetics ◽

10.1093/genetics/155.4.1831 ◽

2000 ◽

Vol 155 (4) ◽

pp. 1831-1839

Author(s):

Emily Harms ◽

Tehyen Chu ◽

Gwénola Henrion ◽

Sidney Strickland

Keyword(s):

Zinc Finger ◽

Transcriptional Activation ◽

Single Amino Acid ◽

Primary Role ◽

Extra Copy ◽

Oocyte Meiosis ◽

Zinc Finger Motifs ◽

High Level ◽

Transcriptional Pathway

Abstract The grauzone and cortex genes are required for the completion of meiosis in Drosophila oocytes. The grauzone gene encodes a C2H2-type zinc-finger transcription factor that binds to the cortex promoter and is necessary for high-level activation of cortex transcription. Here we define the region of the cortex promoter to which Grauzone binds and show that the binding occurs through the C-terminal, zinc-finger-rich region of the protein. Mutations in two out of the five grauzone alleles result in single amino acid changes within different zinc-finger motifs. Both of these mutations result in the inability of Grauzone to bind DNA effectively. To determine the mechanism by which Grauzone regulates meiosis, transgenic flies were produced with an extra copy of the cortex gene in homozygous grauzone females. This transgene rescued the meiosis arrest of embryos from these mutants and allowed their complete development, indicating that activation of cortex transcription is the primary role of Grauzone during Drosophila oogenesis. These experiments further define a new transcriptional pathway that controls the meiotic cell cycle in Drosophila oocytes.

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From cytopenia to leukemia: the role of Gfi1 and Gfi1b in blood formation

Blood ◽

10.1182/blood-2015-06-655043 ◽

2015 ◽

Vol 126 (24) ◽

pp. 2561-2569 ◽

Cited By ~ 51

Author(s):

Tarik Möröy ◽

Lothar Vassen ◽

Brian Wilkes ◽

Cyrus Khandanpour

Keyword(s):

Zinc Finger ◽

Target Genes ◽

Integration Site ◽

Wide Spectrum ◽

Human Leukemia ◽

Specific Expression ◽

Hematopoietic Stem ◽

Proviral Integration Site ◽

Cell Type Specific Expression

AbstractThe DNA-binding zinc finger transcription factors Gfi1 and Gfi1b were discovered more than 20 years ago and are recognized today as major regulators of both early hematopoiesis and hematopoietic stem cells. Both proteins function as transcriptional repressors by recruiting histone-modifying enzymes to promoters and enhancers of target genes. The establishment of Gfi1 and Gfi1b reporter mice made it possible to visualize their cell type–specific expression and to understand their function in hematopoietic lineages. We now know that Gfi1 is primarily important in myeloid and lymphoid differentiation, whereas Gfi1b is crucial for the generation of red blood cells and platelets. Several rare hematologic diseases are associated with acquired or inheritable mutations in the GFI1 and GFI1B genes. Certain patients with severe congenital neutropenia carry mutations in the GFI1 gene that lead to the disruption of the C-terminal zinc finger domains. Other mutations have been found in the GFI1B gene in families with inherited bleeding disorders. In addition, the Gfi1 locus is frequently found to be a proviral integration site in retrovirus-induced lymphomagenesis, and new, emerging data suggest a role of Gfi1 in human leukemia and lymphoma, underlining the role of both factors not only in normal hematopoiesis, but also in a wide spectrum of human blood diseases.

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