Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Virtual screening of peptide and peptidomimetic fragments targeted to inhibit bacterial dithiol oxidase DsbA", "type"=>"journal", "authors"=>[{"first_name"=>"Wilko", "last_name"=>"Duprez", "scopus_author_id"=>"55507613900"}, {"first_name"=>"Prabhakar", "last_name"=>"Bachu", "scopus_author_id"=>"22233647900"}, {"first_name"=>"Martin J.", "last_name"=>"Stoermer", "scopus_author_id"=>"7003679097"}, {"first_name"=>"Stephanie", "last_name"=>"Tay", "scopus_author_id"=>"55926747600"}, {"first_name"=>"Róisín M.", "last_name"=>"McMahon", "scopus_author_id"=>"8601864600"}, {"first_name"=>"David P.", "last_name"=>"Fairlie", "scopus_author_id"=>"7007085404"}, {"first_name"=>"Jennifer L.", "last_name"=>"Martin", "scopus_author_id"=>"56137417200"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84942346095", "doi"=>"10.1371/journal.pone.0133805", "pui"=>"606057610", "pmid"=>"26225423", "scopus"=>"2-s2.0-84942346095", "issn"=>"19326203"}, "id"=>"4cc6aa29-618e-35bb-8527-c43abc621a26", "abstract"=>"Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota) might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB--or peptides--complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a Proteus mirabilis DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an in silico template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.", "link"=>"http://www.mendeley.com/research/virtual-screening-peptide-peptidomimetic-fragments-targeted-inhibit-bacterial-dithiol-oxidase-dsba", "reader_count"=>8, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84942346095"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84942346095?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84942346095&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84942346095&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84942346095", "dc:identifier"=>"SCOPUS_ID:84942346095", "eid"=>"2-s2.0-84942346095", "dc:title"=>"Virtual screening of peptide and peptidomimetic fragments targeted to inhibit bacterial dithiol oxidase DsbA", "dc:creator"=>"Duprez W.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"10", "prism:issueIdentifier"=>"7", "prism:pageRange"=>nil, "prism:coverDate"=>"2015-07-30", "prism:coverDisplayDate"=>"30 July 2015", "prism:doi"=>"10.1371/journal.pone.0133805", "citedby-count"=>"9", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"The University of Queensland", "affiliation-city"=>"Brisbane", "affiliation-country"=>"Australia"}], "pubmed-id"=>"26225423", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e0133805", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0133805", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"6", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"156"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"96"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"52"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"60"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"24"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"84"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"87"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"15"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"2", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"19"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"3", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"20"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"6"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"14"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2020", "pdf_views"=>"27", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"10", "year"=>"2020", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"11", "year"=>"2020", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"8"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2195149"], "description"=>"<p><b>A.</b> Differential scanning fluorimetry profile with increasing concentrations of compound <b>10</b>. Similar to all other compounds tested, there was no significant shift in the unfolding temperature of EcDsbA up to 2 mM of compound <b>10</b>. <b>B.</b> ITC profile of EcDsbA titration by compound <b>10</b>, which shows no detectable binding under the conditions used (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133805#sec002\" target=\"_blank\">methods</a> for details). A similar outcome was found for the other 9 compounds. <b>C.</b> Compound <b>10</b> was the only one of the ten tested peptidomimetics that exhibited detectable activity in the DsbA assay, inducing a reduction in DsbA folding activity. <b>D.</b> Plotting the log of the peptidomimetic concentration against the rate of fluorescence increase measured in the enzyme assay allowed fitting of a sigmoidal curve and an estimated IC<sub>50</sub> value of ~1 mM for compound <b>10</b>. The positive control with no compound is shown as a white circle.</p>", "links"=>[], "tags"=>["site cysteine", "PWATCDS", "Peptidomimetic Fragments Targeted", "covalent peptide inhibitors", "Proteus mirabilis DsbA", "groove", "virulence factor assembly", "Dithiol Oxidase DsbA Antibacterial drugs", "peptidomimetic fragment library"], "article_id"=>1498119, "categories"=>["Biological Sciences"], "users"=>["Wilko Duprez", "Prabhakar Bachu", "Martin J. Stoermer", "Stephanie Tay", "Róisín M. McMahon", "David P. Fairlie", "Jennifer L. Martin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133805.g005", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Compound_10_demonstrated_weak_inhibitory_activity_/1498119", "title"=>"Compound 10 demonstrated weak inhibitory activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-30 03:02:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2195150", "https://ndownloader.figshare.com/files/2195151", "https://ndownloader.figshare.com/files/2195152", "https://ndownloader.figshare.com/files/2195153", "https://ndownloader.figshare.com/files/2195154", "https://ndownloader.figshare.com/files/2195155", "https://ndownloader.figshare.com/files/2195156", "https://ndownloader.figshare.com/files/2195157", "https://ndownloader.figshare.com/files/2195158", "https://ndownloader.figshare.com/files/2195159"], "description"=>"<div><p>Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota) might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB - or peptides - complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a <i>Proteus mirabilis</i> DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an <i>in silico</i> template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.</p></div>", "links"=>[], "tags"=>["site cysteine", "PWATCDS", "Peptidomimetic Fragments Targeted", "covalent peptide inhibitors", "Proteus mirabilis DsbA", "groove", "virulence factor assembly", "Dithiol Oxidase DsbA Antibacterial drugs", "peptidomimetic fragment library"], "article_id"=>1498120, "categories"=>["Biological Sciences"], "users"=>["Wilko Duprez", "Prabhakar Bachu", "Martin J. Stoermer", "Stephanie Tay", "Róisín M. McMahon", "David P. Fairlie", "Jennifer L. Martin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0133805.s001", "https://dx.doi.org/10.1371/journal.pone.0133805.s002", "https://dx.doi.org/10.1371/journal.pone.0133805.s003", "https://dx.doi.org/10.1371/journal.pone.0133805.s004", "https://dx.doi.org/10.1371/journal.pone.0133805.s005", "https://dx.doi.org/10.1371/journal.pone.0133805.s006", "https://dx.doi.org/10.1371/journal.pone.0133805.s007", "https://dx.doi.org/10.1371/journal.pone.0133805.s008", "https://dx.doi.org/10.1371/journal.pone.0133805.s009", "https://dx.doi.org/10.1371/journal.pone.0133805.s010"], "stats"=>{"downloads"=>44, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virtual_Screening_of_Peptide_and_Peptidomimetic_Fragments_Targeted_to_Inhibit_Bacterial_Dithiol_Oxidase_DsbA_/1498120", "title"=>"Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-07-30 03:02:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2195148"], "description"=>"<p>Compound <b>1</b> is the hit from the virtual screening from which derivatives <b>2</b>–<b>10</b> were designed.</p>", "links"=>[], "tags"=>["site cysteine", "PWATCDS", "Peptidomimetic Fragments Targeted", "covalent peptide inhibitors", "Proteus mirabilis DsbA", "groove", "virulence factor assembly", "Dithiol Oxidase DsbA Antibacterial drugs", "peptidomimetic fragment library"], "article_id"=>1498118, "categories"=>["Biological Sciences"], "users"=>["Wilko Duprez", "Prabhakar Bachu", "Martin J. Stoermer", "Stephanie Tay", "Róisín M. McMahon", "David P. Fairlie", "Jennifer L. Martin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133805.g004", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemical_structures_of_the_10_peptidomimetic_compounds_synthesized_and_tested_in_this_work_/1498118", "title"=>"Chemical structures of the 10 peptidomimetic compounds synthesized and tested in this work.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-30 03:02:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2195145"], "description"=>"<p><b>A.</b> Schematic showing the proposed mechanism of oxidative folding in the periplasm of Gram-negative bacteria. DsbA catalyses the formation of a disulfide bond in a protein substrate, then interacts with DsbB to which it transfers electrons so that DsbA is regenerated into its active oxidized state. The electrons are subsequently transferred from DsbB to ubiquinone (UQ) and ultimately to the respiratory complex. <b>B.</b> The binding interface between EcDsbA (black and red) and EcDsbB loop P2 (blue) derived from the crystal structure of the EcDsbAC33A:EcDsbBC130S complex [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133805#pone.0133805.ref037\" target=\"_blank\">37</a>]. The EcDsbA hydrophobic groove residues are highlighted in orange shading, the intermolecular disulfide bond is shown as a solid red line and the hydrogen bond with the <i>cis</i>Pro loop is shown as a dashed red line. <b>C.</b> The binding interface between PmDsbA (black and red) and the peptide PWATCDS (blue) from the crystal structure of the complex [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133805#pone.0133805.ref038\" target=\"_blank\">38</a>]. In this complex there is no disulfide bond as the active site cysteine of PmDsbA was mutated to Ser (S30). The peptide Cys5 residue points away from the binding interface. Residues W2 and P1 of the peptide both interact with the hydrophobic groove (in orange) and these interactions were used as the target for this peptidomimetic design.</p>", "links"=>[], "tags"=>["site cysteine", "PWATCDS", "Peptidomimetic Fragments Targeted", "covalent peptide inhibitors", "Proteus mirabilis DsbA", "groove", "virulence factor assembly", "Dithiol Oxidase DsbA Antibacterial drugs", "peptidomimetic fragment library"], "article_id"=>1498115, "categories"=>["Biological Sciences"], "users"=>["Wilko Duprez", "Prabhakar Bachu", "Martin J. Stoermer", "Stephanie Tay", "Róisín M. McMahon", "David P. Fairlie", "Jennifer L. Martin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133805.g001", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_DsbA_DsbB_interaction_/1498115", "title"=>"The DsbA-DsbB interaction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-30 03:02:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2195147"], "description"=>"<p>Calculated electrostatic surfaces of the enzymes are shown, with acidic regions in red, basic regions in blue and non-polar (hydrophobic) regions in white. Electrostatics cut-offs used are +/- 7.5 keV. <b>A.</b> Detail of the EcDsbA complex with EcDsbB from the crystal structure (PDB code 2ZUP [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133805#pone.0133805.ref037\" target=\"_blank\">37</a>]) centred on the <sup>97</sup>YPSPFATCDFMVR<sup>109</sup> sequence of EcDsbB (in light blue) showing Phe101 (F101) binding in the EcDsbA hydrophobic groove (circled). <b>B.</b> Detail of the PmDsbAC30S:PWATCDS crystal structure (PDB code 4OD7) with PWATCDS in magenta. Residue Trp2 (W2) of the peptide binds in the PmDsbA hydrophobic groove (circled). <b>C.</b> Virtual screening identified compound <b>1</b> as a potential hit. Three optimal conformations of <b>1</b> are shown (in differing shades of green), in their predicted binding mode to the PmDsbAC30S hydrophobic groove. Potential hydrogen bonds between the morpholine moiety and DsbA Pro150, His32 and Asn162 are shown as yellow dashed lines.</p>", "links"=>[], "tags"=>["site cysteine", "PWATCDS", "Peptidomimetic Fragments Targeted", "covalent peptide inhibitors", "Proteus mirabilis DsbA", "groove", "virulence factor assembly", "Dithiol Oxidase DsbA Antibacterial drugs", "peptidomimetic fragment library"], "article_id"=>1498117, "categories"=>["Biological Sciences"], "users"=>["Wilko Duprez", "Prabhakar Bachu", "Martin J. Stoermer", "Stephanie Tay", "Róisín M. McMahon", "David P. Fairlie", "Jennifer L. Martin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133805.g003", "stats"=>{"downloads"=>6, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_the_docked_designed_peptidomimetic_with_the_EcDsbA_EcDsbB_and_PmDsbA_PWATCDS_crystal_structures_/1498117", "title"=>"Comparison of the docked designed peptidomimetic with the EcDsbA-EcDsbB and PmDsbA-PWATCDS crystal structures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-30 03:02:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2195146"], "description"=>"<p>Synthetic route for the tripeptide peptidomimetics.</p>", "links"=>[], "tags"=>["site cysteine", "PWATCDS", "Peptidomimetic Fragments Targeted", "covalent peptide inhibitors", "Proteus mirabilis DsbA", "groove", "virulence factor assembly", "Dithiol Oxidase DsbA Antibacterial drugs", "peptidomimetic fragment library"], "article_id"=>1498116, "categories"=>["Biological Sciences"], "users"=>["Wilko Duprez", "Prabhakar Bachu", "Martin J. Stoermer", "Stephanie Tay", "Róisín M. McMahon", "David P. Fairlie", "Jennifer L. Martin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0133805.g002", "stats"=>{"downloads"=>9, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Synthetic_route_for_the_tripeptide_peptidomimetics_/1498116", "title"=>"Synthetic route for the tripeptide peptidomimetics.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-30 03:02:24"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"20", "full-text"=>"22", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"21", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"11", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"13", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"14", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
Loading … Spinner
There are currently no alerts