Crystal structure of the protease‐resistant core domain of <i>Yersinia pestis</i> virulence factor YopR

Schubot, Florian D.; Cherry, Scott; Austin, Brian; Tropea, Joseph E.; Waugh, David S.

doi:10.1110/ps.051446405

Cited by 6 publications

(2 citation statements)

References 27 publications

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“…и соавт. [142] исследовали кристаллическую структуру резистентного к протеа-зам домена кора YopR (38-149 аминокислотные остатки) и обнаружили в этой области пять альфа-спиралей. Структура рассматриваемой области оказалась подобна структуре одного из доменов центрального регулятора T3SS Y. pestis YopN.…”

Section: эффекторные Yop-белкиunclassified

A search for new molecular targets for optimizing plague preventive vaccination and therapy

Красильникова

Трунякова

Вагайская

et al. 2020

Russian Journal of Infection and Immunity

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The causative agent of plague, Yersinia pestis, is a highly virulent bacterial pathogen and a potential bioweapon. Depending on the route of infection, two prevalent forms of the disease – bubonic and pneumonic, are known. The latter is featured by a high fatality rate. Mortality in untreated bubonic plague patients reaches up to 40-60%, whereas untreated pneumonic plague is always lethal. The development of the infectious process in susceptible host is accounted for by a whole set of pathogenicity factors in plaque pathogen displaying various functional modalities being expressed depending on stage of infectious process, providing their coordinated expression. Knocking out any of such factors, in turn, may not either affect microbe virulence or lead to its attenuation. A search for new Yersinia pestis pathogenicity factors and subsequent development of highly effective subunit and live attenuated plague vaccines inducing development of pronounced cellular and humoral immune reactions, and/or assessment of their potential use as molecular targets for plague therapy still remain a pressing issue, as both currently licensed plague vaccines do not meet the WHO requirements, whereas strains of plague microbe isolated in Madagascar are resistant to all drugs recommended for plague antibacterial therapy. Here we summarize an impact of described and newly discovered pathogenicity factors into the virulence of Y. pestis strains and their protective anti-plague activity. An effect of loss of genes encoding regulatory proteins as well as mutations in the genes for various transport systems of Y. pestis on attenuation of virulent strains is described as well. Perspectives for introducing characterized antigens into prototype subunit vaccine as well as some other obtained mutants into prototypes of living attenuating vaccines were assessed. The use of antibiotics for plague treatment has been embraced by the World Health Organization Expert Committee on Plague as the ‘gold standard’ treatment. However, concerns regarding development of antibiotic-resistant Y. pestis strains accounted for further exploring alternatives to plaque therapy. Several research groups continue working on seeking for other alternative approaches, e.g. treatment with inhibitors of pathogenicity factors. Preliminary data attempting to treat plague patients with pathogenicity factor inhibitors are summarized. Аnti-virulence drugs targeting key microbial factors represent new promising therapeutic options in fight against antibiotic-resistant bacteria.

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Section: эффекторные Yop-белкиunclassified

A search for new molecular targets for optimizing plague preventive vaccination and therapy

Красильникова

Трунякова

Вагайская

et al. 2020

Russian Journal of Infection and Immunity

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“…As an example, the YopR protein was crystallized and shown to be structurally similar to YopN [62], but it took another five years to elucidate the critical role that YopR assumes in the assembly of Yersinia YopF needle subunits into a functional needle [63]. With the YopR structure in hand and genetic data to demonstrate the essential nature of this protein to the Yersinia T3SS, the transition can be made from protein of interest to protein drug target.…”

Section: Inner Membranementioning

confidence: 99%

The Type III Secretion System as a Source of Novel Antibacterial Drug Targets

Kline¹,

Felise²,

Sanowar³

et al. 2012

CDT

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Type III Secretion Systems (T3SSs) are highly organized multi-protein nanomachines which translocate effector proteins from the bacterial cytosol directly into host cells. These systems are required for the pathogenesis of a wide array of Gram-negative bacterial pathogens, and thus have attracted attention as potential antibacterial drug targets. A decade of research has enabled the identification of natural products, conventional small molecule drug-like structures, and proteins that inhibit T3SSs. The mechanism(s) of action and molecular target(s) of the majority of these inhibitors remain to be determined. At the same time, structural biology methods are providing an increasingly detailed picture of the functional arrangement of the T3SS component proteins. The confluence of these two research areas may ultimately identify non-classical drug targets and facilitate the development of novel therapeutics.

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In vivo cleavage of solubility tags as a tool to enhance the levels of soluble recombinant proteins in Escherichia coli

Silva

Santos

Meyer

et al. 2021

Biotech & Bioengineering

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Recombinant proteins are generally fused with solubility enhancer tags to improve the folding and solubility of the target protein of interest. However, the fusion protein strategy usually requires expensive proteases to perform in vitro proteolysis and additional chromatographic steps to obtain tag-free recombinant proteins.Expression systems based on intracellular processing of solubility tags in Escherichia coli, through co-expression of a site-specific protease, simplify the recombinant protein purification process, and promote the screening of molecules that fail to remain soluble after tag removal. High yields of soluble target proteins have already been achieved using these protease co-expression systems. Herein, we review approaches for controlled intracellular processing systems tailored to produce soluble untagged proteins in E. coli. We discuss the different genetic systems available for intracellular processing of recombinant proteins regarding system design features, advantages, and limitations of the various strategies.

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Crystal structure of the protease‐resistant core domain of Yersinia pestis virulence factor YopR

Cited by 6 publications

References 27 publications

A search for new molecular targets for optimizing plague preventive vaccination and therapy

A search for new molecular targets for optimizing plague preventive vaccination and therapy

The Type III Secretion System as a Source of Novel Antibacterial Drug Targets

In vivo cleavage of solubility tags as a tool to enhance the levels of soluble recombinant proteins in Escherichia coli

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