Cobalt(<scp>ii</scp>) cation binding by proteins

Khrustalev, Vladislav Victorovich; Khrustaleva, Tatyana Aleksandrovna; Poboinev, Victor Vitoldovich; Karchevskaya, Carolina Igorevna; Shablovskaya, Elizaveta Aleksandrovna; Terechova, Tatyana Germanovna

doi:10.1039/c9mt00205g

Cited by 11 publications

(6 citation statements)

References 26 publications

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“…The ionic radius of Co 2+ is 0.76 Å, which is similar to 0.74 Å of Zn 2+ , 0.69 Å for Cu 2+ , and 0.76 Å for Fe 2+ . Additionally, based on the available Protein Data Bank structures with Co 2+ , the study Khrustalev et al ( 2019 ) found that Co 2+ is commonly bound by cation traps. The traps are formed by relatively negatively charged regions of random coil between a β stand and α helix and between two β strands in which His, Asp, and Glu residues are situated.…”

Section: Cobalt Coenzymes and Proteinsmentioning

confidence: 99%

Cobalt: An Essential Micronutrient for Plant Growth?

et al. 2021

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Cobalt is a transition metal located in the fourth row of the periodic table and is a neighbor of iron and nickel. It has been considered an essential element for prokaryotes, human beings, and other mammals, but its essentiality for plants remains obscure. In this article, we proposed that cobalt (Co) is a potentially essential micronutrient of plants. Co is essential for the growth of many lower plants, such as marine algal species including diatoms, chrysophytes, and dinoflagellates, as well as for higher plants in the family Fabaceae or Leguminosae. The essentiality to leguminous plants is attributed to its role in nitrogen (N) fixation by symbiotic microbes, primarily rhizobia. Co is an integral component of cobalamin or vitamin B12, which is required by several enzymes involved in N2 fixation. In addition to symbiosis, a group of N2 fixing bacteria known as diazotrophs is able to situate in plant tissue as endophytes or closely associated with roots of plants including economically important crops, such as barley, corn, rice, sugarcane, and wheat. Their action in N2 fixation provides crops with the macronutrient of N. Co is a component of several enzymes and proteins, participating in plant metabolism. Plants may exhibit Co deficiency if there is a severe limitation in Co supply. Conversely, Co is toxic to plants at higher concentrations. High levels of Co result in pale-colored leaves, discolored veins, and the loss of leaves and can also cause iron deficiency in plants. It is anticipated that with the advance of omics, Co as a constitute of enzymes and proteins and its specific role in plant metabolism will be exclusively revealed. The confirmation of Co as an essential micronutrient will enrich our understanding of plant mineral nutrition and improve our practice in crop production.

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Section: Cobalt Coenzymes and Proteinsmentioning

confidence: 99%

Cobalt: An Essential Micronutrient for Plant Growth?

et al. 2021

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“…Conjugative plasmids encode T4SS primases like TraC of RP4 that contain metallopeptidase domains and relaxases like TraI of RP4 that contain magnesium-binding sites. Cobalt(II) can occupy the same binding site as magnesium or manganese to form different coordination bonds and alter the properties of an active centre 57 . Hence, cobalt complexes may target metal-binding T4SS proteins and interfere with their function.…”

Section: Discussionmentioning

confidence: 99%

Cobalt complexes modulate plasmid conjugation in Escherichia coli and Klebsiella pneumoniae

Alav,

Pordelkhaki,

de Resende

et al. 2024

Sci Rep

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Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Cobalt complexes possess diverse biological activities, including antimicrobial and anticancer properties. However, their effect on plasmid conjugation has not been explored yet. Here, we assessed the effect of four previously characterised bis(N-picolinamido)cobalt(II) complexes lacking antibacterial activity on plasmid conjugation in Escherichia coli and Klebsiella pneumoniae. Antimicrobial susceptibility testing of these cobalt complexes confirmed the lack of antibacterial activity in E. coli and K. pneumoniae. Liquid broth and solid agar conjugation assays were used to screen the activity of the complexes on four archetypical plasmids in E. coli J53. The cobalt complexes significantly reduced the conjugation of RP4, R6K, and R388 plasmids, but not pKM101, on solid agar in E. coli J53. Owing to their promising activity, the impact of cobalt complexes was tested on the conjugation of fluorescently tagged extended-spectrum β-lactamase encoding pCTgfp plasmid in E. coli and carbapenemase encoding pKpQILgfp plasmid in K. pneumoniae, using flow cytometry. The complexes significantly reduced the conjugation of pKpQILgfp in K. pneumoniae but had no impact on pCTgfp conjugation in E. coli. The cobalt complexes did not have plasmid-curing activity, suggesting that they target conjugation rather than plasmid stability. To our knowledge, this is the first study to report reduced conjugation of clinically relevant plasmids with cobalt complexes. These cobalt complexes are not cytotoxic towards mammalian cells and are not antibacterial, therefore they could be optimised and employed as inhibitors of plasmid conjugation.

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“…Lastly, it is worthwhile to point out that substituting zinc ions with cobalt ions is a very useful tool to explore the catalytic properties of enzymes (Kobayashi and Shimizu, 1999). Cobalt is an essential cofactor in many cellular functions (Kobayashi and Shimizu, 1999;Heffern et al, 2013;Khrustalev et al, 2019), but it can also restore the activity of many enzymes in the absence of zinc ions and even accelerate enzyme activity (Fukasawa et al, 2011). However, when working with cells, attention should be paid to the ingredients in the media, since it has been reported that e.g., DMEM has a higher content of histidine, which can chelate cobalt ions, compared to RPMI 1640 and DMEM/ F12 mediums, which seems to be a better choice for cobaltrelated studies, in which growing media is required (Torii et al, 2011).…”

Section: Figurementioning

confidence: 99%

Aminopeptidase B can bioconvert L-type amino acid transporter 1 (LAT1)-utilizing amide prodrugs in the brain

Hugele

Löffler²,

Molina³

et al. 2022

Front. Pharmacol.

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A prodrug approach is a powerful method to temporarily change the physicochemical and thus, pharmacokinetic properties of drugs. However, in site-selective targeted prodrug delivery, tissue or cell-specific bioconverting enzyme is needed to be utilized to release the active parent drug at a particular location. Unfortunately, ubiquitously expressed enzymes, such as phosphatases and carboxylesterases are well used in phosphate and ester prodrug applications, but less is known about enzymes selectively expressed, e.g., in the brain and enzymes that can hydrolyze more stable prodrug bonds, such as amides and carbamates. In the present study, L-type amino acid transporter 1 (LAT1)-utilizing amide prodrugs bioconverting enzyme was identified by gradually exploring the environment and possible determinants, such as pH and metal ions, that affect amide prodrug hydrolysis. Based on inducement by cobalt ions and slightly elevated pH (8.5) as well as localization in plasma, liver, and particularly in the brain, aminopeptidase B was proposed to be responsible for the bioconversion of the majority of the studied amino acid amide prodrugs. However, this enzyme hydrolyzed only those prodrugs that contained an aromatic promoiety (L-Phe), while leaving the aliphatic promoeities (L-Lys) and the smallest prodrug (with L-Phe promoiety) intact. Moreover, the parent drugs’ structure (flexibility and the number of aromatic rings) largely affected the bioconversion rate. It was also noticed in this study, that there were species differences in the bioconversion rate by aminopeptidase B (rodents > human), although the in vitro–in vivo correlation of the studied prodrugs was relatively accurate.

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Cobalt(ii) cation binding by proteins

Abstract: Herein, a set of non-homologous proteins (238) that could bind the cobalt(ii) cations was selected from all the available Protein Data Bank structures with Co2+ cations.

Cited by 11 publications

References 26 publications

Cobalt: An Essential Micronutrient for Plant Growth?

Cobalt: An Essential Micronutrient for Plant Growth?

Cobalt complexes modulate plasmid conjugation in Escherichia coli and Klebsiella pneumoniae

Aminopeptidase B can bioconvert L-type amino acid transporter 1 (LAT1)-utilizing amide prodrugs in the brain

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