scholarly journals Metal binding spectrum and model structure of theBacillus anthracisvirulence determinant MntA

Metallomics ◽  
2015 ◽  
Vol 7 (10) ◽  
pp. 1407-1419 ◽  
Author(s):  
Elena Vigonsky ◽  
Inbar Fish ◽  
Nurit Livnat-Levanon ◽  
Elena Ovcharenko ◽  
Nir Ben-Tal ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Metal Binding ◽  
Model Structure ◽  
High Affinity ◽  
Virulence Determinant ◽  
System P

TheBacillus anthracisvirulence determinant MntA is a high-affinity manganese system.

A consensus zinc finger peptide: design, high-affinity metal binding, a pH-dependent structure, and a His to Cys sequence variant

1991 ◽  
Vol 113 (12) ◽  
pp. 4518-4523 ◽  
Author(s):  
Beth Allyn Krizek ◽  
Barbara T. Amann ◽  
Valda J. Kilfoil ◽  
Denise L. Merkle ◽  
Jeremy M. Berg
Keyword(s):  
Zinc Finger ◽  
Metal Binding ◽  
Sequence Variant ◽  
Peptide Design ◽  
High Affinity ◽  
Ph Dependent ◽  
Zinc Finger Peptide

Design and applications of methods for fluorescence detection of iron in biological systems

2002 ◽  
Vol 30 (4) ◽  
pp. 729-732 ◽  
Author(s):  
B. P. Espósito ◽  
W. Breuer ◽  
Z. I. Cabantchik
Keyword(s):  
Metal Binding ◽  
Biological Systems ◽  
Iron Chelator ◽  
Specific Cell ◽  
Iron Binding ◽  
Physiological Conditions ◽  
High Affinity ◽  
Cell Compartments ◽  
Heterogeneous Nature ◽  
Labile Iron

Fluorescence metalosensors provide a means to detect iron in biological systems that is versatile, economical, sensitive and of a high-throughput nature. They rely on relatively high-affinity iron-binding carriers conjugated to highly fluorescent probes that undergo quenching after metal complexation. Metal specificity is determined by probes containing either an iron-binding moiety of high affinity (type A) or of relatively lower affinity (type B) used in combination with a strong specific iron chelator. Due to the heterogeneous nature of biological systems, the apparent metal-binding affinity and complexation stoichiometry ought to be specifically defined. Fluoresceinated moieties coupled to metal-binding cores detect Fe at sub-micromolar concentrations and even sub-microlitre volumes (i.e. cells). Although an ideal probe should also be specific for a particular oxidation state of iron, in physiological conditions that property might be difficult to attain. Quantification of labile iron in cells has relied on the ability of permeant iron chelators to restore the fluorescence of probes quenched by intracellular Fe. Modern design of probes aims to (a) improve probe targeting to specific cell compartments and (b) create probes that respond to metal binding by signal enhancement.

Characterization of Ligands of a High-Affinity Metal-Binding Site in the Latent Chloroplast F1-ATPase by EPR Spectroscopy of Bound VO2+

Biochemistry ◽  
1994 ◽  
Vol 33 (16) ◽  
pp. 4910-4917 ◽  
Author(s):  
Andrew L. P. Houseman ◽  
Lola Morgan ◽  
Russell LoBrutto ◽  
Wayne D. Frasch
Keyword(s):  
Binding Site ◽  
Epr Spectroscopy ◽  
Metal Binding ◽  
Metal Binding Site ◽  
F1 Atpase ◽  
High Affinity

scholarly journals Effects of Multiple Metal Binding Sites on Calcium and Magnesium-dependent Activation of BK Channels

2005 ◽  
Vol 127 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Lei Hu ◽  
Huanghe Yang ◽  
Jingyi Shi ◽  
Jianmin Cui
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
Quantitative Estimation ◽  
Bk Channels ◽  
Channel Activation ◽  
Metal Binding Sites ◽  
High Affinity ◽  
A Site ◽  
Metal Sensing ◽  
Allosteric Model

BK channels are activated by physiological concentrations of intracellular Ca2+ and Mg2+ in a variety of cells. Previous studies have identified two sites important for high-affinity Ca2+ sensing between [Ca2+]i of 0.1–100 μM and a site important for Mg2+ sensing between [Mg2+]i of 0.1–10 mM. BK channels can be also activated by Ca2+ and Mg2+ at concentrations >10 mM so that the steady-state conductance and voltage (G-V) relation continuously shifts to more negative voltage ranges when [Mg2+]i increases from 0.1–100 mM. We demonstrate that a novel site is responsible for metal sensing at concentrations ≥10 mM, and all four sites affect channel activation independently. As a result, the contributions of these sites to channel activation are complex, depending on the combination of Ca2+ and Mg2+ concentrations. Here we examined the effects of each of these sites on Ca2+ and Mg2+-dependent activation and the data are consistent with the suggestion that these sites are responsible for metal binding. We provide an allosteric model for quantitative estimation of the contributions that each of these putative binding sites makes to channel activation at any [Ca2+]i and [Mg2+]i.

scholarly journals The salivary, metal-binding peptide histatin-5 buffers extracellular copper availability

2022 ◽  
Author(s):  
Louisa Stewart ◽  
YoungJin Hong ◽  
Isabel Holmes ◽  
Samantha Firth ◽  
Jack Bolton ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Metal Binding ◽  
Group A Streptococcus ◽  
Negative Effects ◽  
Histatin 5 ◽  
High Affinity ◽  
Nutritional Immunity ◽  
Zn Uptake ◽  
Inducible Genes ◽  
Zn Availability

The family of human salivary histidine-rich peptides known as histatins bind zinc (Zn) and copper (Cu), but whether they contribute to nutritional immunity by influencing Zn and/or Cu availability has not been examined. We hypothesised that histatin-5 (Hst5) limits Zn availability (and promotes bacterial Zn starvation) and/or raises Cu availability (and promotes bacterial Cu poisoning). To test this hypothesis, Group A Streptococcus (GAS), which colonises the human oropharynx, was used as a model bacterium. Contrary to our hypothesis, Hst5 did not strongly influence Zn availability. This peptide did not induce expression of Zn uptake genes in GAS, nor did it suppress growth of an ΔadcAI mutant strain that is impaired in Zn uptake. Equilibrium competition measurements confirmed that Hst5 binds Zn weakly and does not compete with the high-affinity Zn uptake protein AdcAI for binding Zn. By contrast, Hst5 bound Cu with a high affinity and strongly influenced Cu availability. However, contrary to our hypothesis, Hst5 did not promote Cu toxicity. Instead, this peptide suppressed expression of Cu-inducible genes in GAS, stopped intracellular accumulation of Cu, and rescued growth of a ΔcopA mutant strain that is impaired in Cu efflux in the presence of added Cu. These findings led us to propose a new role for Hst5 and salivary histatins as major Cu buffers in saliva that reduce the potential negative effects of Cu exposure to microbes. We speculate that histatins promote oral and oropharyngeal health by contributing to microbial homeostasis in these host niches.

High-Affinity Metal-Binding Site in Beef Heart Mitochondrial F1ATPase:  An EPR Spectroscopy Study†

Biochemistry ◽  
2004 ◽  
Vol 43 (41) ◽  
pp. 13214-13224 ◽  
Author(s):  
Alfonso Zoleo ◽  
Stefania Contessi ◽  
Giovanna Lippe ◽  
Luca Pinato ◽  
Marina Brustolon ◽  
...  
Keyword(s):  
Binding Site ◽  
Epr Spectroscopy ◽  
Metal Binding ◽  
Beef Heart ◽  
Spectroscopy Study ◽  
Metal Binding Site ◽  
High Affinity

scholarly journals Role for dithiolopyrrolones in disrupting bacterial metal homeostasis

2017 ◽  
Vol 114 (10) ◽  
pp. 2717-2722 ◽  
Author(s):  
Andrew N. Chan ◽  
Anthony L. Shiver ◽  
Walter J. Wever ◽  
Sayyeda Zeenat A. Razvi ◽  
Matthew F. Traxler ◽  
...  
Keyword(s):  
Natural Products ◽  
Rna Polymerase ◽  
Metal Binding ◽  
Antimicrobial Activities ◽  
Metal Homeostasis ◽  
Chemical Genomics ◽  
Chemical Structures ◽  
High Affinity ◽  
Metal Chelating

Natural products harbor unique and complex structures that provide valuable antibiotic scaffolds. With an increase in antibiotic resistance, natural products once again hold promise for new antimicrobial therapies, especially those with unique scaffolds that have been overlooked due to a lack of understanding of how they function. Dithiolopyrrolones (DTPs) are an underexplored class of disulfide-containing natural products, which exhibit potent antimicrobial activities against multidrug-resistant pathogens. DTPs were thought to target RNA polymerase, but conflicting observations leave the mechanisms elusive. Using a chemical genomics screen inEscherichia coli, we uncover a mode of action for DTPs—the disruption of metal homeostasis. We show that holomycin, a prototypical DTP, is reductively activated, and reduced holomycin chelates zinc with high affinity. Examination of reduced holomycin against zinc-dependent metalloenzymes revealed that it inhibitsE. coliclass II fructose bisphosphate aldolase, but not RNA polymerase. Reduced holomycin also strongly inhibits metallo–β-lactamases in vitro, major contributors to clinical carbapenem resistance, by removing active site zinc. These results indicate that holomycin is an intracellular metal-chelating antibiotic that inhibits a subset of metalloenzymes and that RNA polymerase is unlikely to be the primary target. Our work establishes a link between the chemical structures of DTPs and their antimicrobial action; the ene-dithiol group of DTPs enables high-affinity metal binding as a central mechanism to inhibit metabolic processes. Our study also validates the use of chemical genomics in characterizing modes of actions of antibiotics and emphasizes the potential of metal-chelating natural products in antimicrobial therapy.

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