Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-07

AUTHORS

Aimee Shen, Patrick J Lupardus, Victoria E Albrow, Andrew Guzzetta, James C Powers, K Christopher Garcia, Matthew Bogyo

ABSTRACT

MARTX toxins modulate the virulence of a number of Gram-negative Vibrio species. This family of toxins is defined by the presence of a cysteine protease domain (CPD), which proteolytically activates the Vibrio cholerae MARTX toxin. Although recent structural studies of the CPD have uncovered a new allosteric activation mechanism, the mechanism of CPD substrate recognition or toxin processing is unknown. Here we show that interdomain cleavage of MARTXVc enhances effector domain function. We also identify the first small-molecule inhibitors of this protease domain and present the 2.35-A structure of the CPD bound to one of these inhibitors. This structure, coupled with biochemical and mutational studies of the toxin, reveals the molecular basis of CPD substrate specificity and underscores the evolutionary relationship between the CPD and the clan CD caspase proteases. These studies are likely to prove valuable for devising new antitoxin strategies for a number of bacterial pathogens. More... »

PAGES

469

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nchembio.178

DOI

http://dx.doi.org/10.1038/nchembio.178

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028617423

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19465933


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Allosteric Regulation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Amino Acid Sequence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Blotting, Western", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Catalytic Domain", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cholera Toxin", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Crystallography, X-Ray", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cysteine Proteases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cysteine Proteinase Inhibitors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Enzyme Activation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Molecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Molecular Sequence Data", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Binding", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Structure, Secondary", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Sequence Alignment", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Spectroscopy, Fourier Transform Infrared", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Substrate Specificity", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Vibrio cholerae", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Department of Pathology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shen", 
        "givenName": "Aimee", 
        "id": "sg:person.0633741155.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633741155.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lupardus", 
        "givenName": "Patrick J", 
        "id": "sg:person.01214322055.04", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214322055.04"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Department of Pathology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Albrow", 
        "givenName": "Victoria E", 
        "id": "sg:person.0711630252.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0711630252.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Department of Pathology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Guzzetta", 
        "givenName": "Andrew", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Georgia Institute of Technology", 
          "id": "https://www.grid.ac/institutes/grid.213917.f", 
          "name": [
            "Department of Chemistry, Georgia Institute of Technology, Atlanta, Georgia, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Powers", 
        "givenName": "James C", 
        "id": "sg:person.01016560766.59", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016560766.59"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Garcia", 
        "givenName": "K Christopher", 
        "id": "sg:person.0605144355.92", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605144355.92"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford University", 
          "id": "https://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Department of Pathology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Bogyo", 
        "givenName": "Matthew", 
        "id": "sg:person.07456715137.22", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07456715137.22"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1093/emboj/18.20.5453", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005207646"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/emboj/18.20.5453", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005207646"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature05622", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008166667", 
          "https://doi.org/10.1038/nature05622"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/sj.emboj.7601700", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009667657"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/cr010182v", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009807257"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/cr010182v", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009807257"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jcm.00349-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010971298"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m803334200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010981441"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0021889807021206", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012753217"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00508-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013536332"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-3-642-59605-6_4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014832933", 
          "https://doi.org/10.1007/978-3-642-59605-6_4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-3-642-59605-6_4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014832933", 
          "https://doi.org/10.1007/978-3-642-59605-6_4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0401104101", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016250027"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1462-5822.2006.00876.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016651505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio707", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016969866", 
          "https://doi.org/10.1038/nchembio707"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio707", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016969866", 
          "https://doi.org/10.1038/nchembio707"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio707", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016969866", 
          "https://doi.org/10.1038/nchembio707"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00525-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017607791"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.01503-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018047230"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1515/bc.2001.088", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019407825"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444998003254", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019779527"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444904019158", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020281098"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444996012255", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020405374"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bj3500563", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020851826"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bj3500563", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020851826"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444903008126", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031860267"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00506-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040079016"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt1408", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041621508", 
          "https://doi.org/10.1038/nbt1408"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.00045-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041728681"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.micinf.2004.03.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042870090"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio.70", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044068305", 
          "https://doi.org/10.1038/nchembio.70"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/iai.01308-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045818820"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m703062200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047896444"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1515/bchm.2001.382.5.727", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050575154"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkm216", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052481822"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi060364p", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055201845"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi060364p", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055201845"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm025581c", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055947825"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm025581c", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055947825"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/0264-6021:3500563", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1056714963"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/dna.2008.0737", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059252259"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1099/jmm.0.47742-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060393590"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1162403", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062458569"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1077413995", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082745710", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2009-07", 
    "datePublishedReg": "2009-07-01", 
    "description": "MARTX toxins modulate the virulence of a number of Gram-negative Vibrio species. This family of toxins is defined by the presence of a cysteine protease domain (CPD), which proteolytically activates the Vibrio cholerae MARTX toxin. Although recent structural studies of the CPD have uncovered a new allosteric activation mechanism, the mechanism of CPD substrate recognition or toxin processing is unknown. Here we show that interdomain cleavage of MARTXVc enhances effector domain function. We also identify the first small-molecule inhibitors of this protease domain and present the 2.35-A structure of the CPD bound to one of these inhibitors. This structure, coupled with biochemical and mutational studies of the toxin, reveals the molecular basis of CPD substrate specificity and underscores the evolutionary relationship between the CPD and the clan CD caspase proteases. These studies are likely to prove valuable for devising new antitoxin strategies for a number of bacterial pathogens.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nchembio.178", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2699532", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2501621", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1327431", 
        "issn": [
          "1552-4450", 
          "1552-4469"
        ], 
        "name": "Nature Chemical Biology", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "5"
      }
    ], 
    "name": "Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin", 
    "pagination": "469", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "8852ecee9f908b949d5bed97c0a641b5aad11f0306f0934b543f6cdbad9362c3"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "19465933"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101231976"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nchembio.178"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1028617423"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nchembio.178", 
      "https://app.dimensions.ai/details/publication/pub.1028617423"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T09:20", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000339_0000000339/records_109514_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nchembio.178"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nchembio.178'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nchembio.178'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nchembio.178'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nchembio.178'


 

This table displays all metadata directly associated to this object as RDF triples.

300 TRIPLES      21 PREDICATES      83 URIs      38 LITERALS      26 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nchembio.178 schema:about N0f159bf99ebd4c49a8f96107f9a97e1e
2 N1853f417ea184da5aa4f8ccfa752185c
3 N1c347748e1ec4aa69f9ea3d183022fe5
4 N30ca6649f4e3442fa208affdd5477621
5 N3374e8b87bf649eba35b6ce89955a6b3
6 N3647cbb3035a4b08b3c81fe377a6ff72
7 N42fb3aabe0f44589a062ac5c552a108c
8 N4c638d6d6a4646ec9ae09cdae99cd781
9 N5074437ba8ff4661aad0c8e7756f2608
10 N7463c1d6cf7846d5b7bbfcdad4f28bbe
11 N81d950a9777e4b03ba6f08d637181af1
12 N928588be187d4166a8c8d0159ea93b2e
13 N96ce6953745b470899b3874caf970ddb
14 Na884f0978a6747088cee33c27c68b69b
15 Naaf7835af8e54daeb52074c70895f37b
16 Ncbbcc0acbfb244fba5f4f1ee55b352ae
17 Ndc9249f4df3a419e95576be80bdda045
18 anzsrc-for:06
19 anzsrc-for:0601
20 schema:author N84d1b2f2929c4d30aa7ecccd8262235e
21 schema:citation sg:pub.10.1007/978-3-642-59605-6_4
22 sg:pub.10.1038/nature05622
23 sg:pub.10.1038/nbt1408
24 sg:pub.10.1038/nchembio.70
25 sg:pub.10.1038/nchembio707
26 https://app.dimensions.ai/details/publication/pub.1077413995
27 https://app.dimensions.ai/details/publication/pub.1082745710
28 https://doi.org/10.1016/j.micinf.2004.03.001
29 https://doi.org/10.1021/bi060364p
30 https://doi.org/10.1021/cr010182v
31 https://doi.org/10.1021/jm025581c
32 https://doi.org/10.1038/sj.emboj.7601700
33 https://doi.org/10.1042/0264-6021:3500563
34 https://doi.org/10.1042/bj3500563
35 https://doi.org/10.1073/pnas.0401104101
36 https://doi.org/10.1074/jbc.m703062200
37 https://doi.org/10.1074/jbc.m803334200
38 https://doi.org/10.1089/dna.2008.0737
39 https://doi.org/10.1093/emboj/18.20.5453
40 https://doi.org/10.1093/nar/gkm216
41 https://doi.org/10.1099/jmm.0.47742-0
42 https://doi.org/10.1107/s0021889807021206
43 https://doi.org/10.1107/s0907444903008126
44 https://doi.org/10.1107/s0907444904019158
45 https://doi.org/10.1107/s0907444996012255
46 https://doi.org/10.1107/s0907444998003254
47 https://doi.org/10.1111/j.1462-5822.2006.00876.x
48 https://doi.org/10.1126/science.1162403
49 https://doi.org/10.1128/iai.00045-07
50 https://doi.org/10.1128/iai.00506-07
51 https://doi.org/10.1128/iai.00508-07
52 https://doi.org/10.1128/iai.00525-07
53 https://doi.org/10.1128/iai.01308-07
54 https://doi.org/10.1128/iai.01503-07
55 https://doi.org/10.1128/jcm.00349-07
56 https://doi.org/10.1515/bc.2001.088
57 https://doi.org/10.1515/bchm.2001.382.5.727
58 schema:datePublished 2009-07
59 schema:datePublishedReg 2009-07-01
60 schema:description MARTX toxins modulate the virulence of a number of Gram-negative Vibrio species. This family of toxins is defined by the presence of a cysteine protease domain (CPD), which proteolytically activates the Vibrio cholerae MARTX toxin. Although recent structural studies of the CPD have uncovered a new allosteric activation mechanism, the mechanism of CPD substrate recognition or toxin processing is unknown. Here we show that interdomain cleavage of MARTXVc enhances effector domain function. We also identify the first small-molecule inhibitors of this protease domain and present the 2.35-A structure of the CPD bound to one of these inhibitors. This structure, coupled with biochemical and mutational studies of the toxin, reveals the molecular basis of CPD substrate specificity and underscores the evolutionary relationship between the CPD and the clan CD caspase proteases. These studies are likely to prove valuable for devising new antitoxin strategies for a number of bacterial pathogens.
61 schema:genre research_article
62 schema:inLanguage en
63 schema:isAccessibleForFree true
64 schema:isPartOf N4bdbe89209e947ccbec387f72f7116be
65 N826d9e889bd0415ea875cf47a7ebd740
66 sg:journal.1327431
67 schema:name Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin
68 schema:pagination 469
69 schema:productId N00ae3ce0d8fc4f2ba37e8969998312d7
70 N11173939140643f68101602b15f857d5
71 N2391d395dc504888992e0864724eba72
72 N2d0739799e814b4aaa7b405bfcdcd389
73 Na425718eb1b149fca03a8e14ed9209a9
74 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028617423
75 https://doi.org/10.1038/nchembio.178
76 schema:sdDatePublished 2019-04-11T09:20
77 schema:sdLicense https://scigraph.springernature.com/explorer/license/
78 schema:sdPublisher Ndf482073f42a4cfaa51e80336846e89a
79 schema:url https://www.nature.com/articles/nchembio.178
80 sgo:license sg:explorer/license/
81 sgo:sdDataset articles
82 rdf:type schema:ScholarlyArticle
83 N00ae3ce0d8fc4f2ba37e8969998312d7 schema:name nlm_unique_id
84 schema:value 101231976
85 rdf:type schema:PropertyValue
86 N0f159bf99ebd4c49a8f96107f9a97e1e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
87 schema:name Allosteric Regulation
88 rdf:type schema:DefinedTerm
89 N11173939140643f68101602b15f857d5 schema:name readcube_id
90 schema:value 8852ecee9f908b949d5bed97c0a641b5aad11f0306f0934b543f6cdbad9362c3
91 rdf:type schema:PropertyValue
92 N1853f417ea184da5aa4f8ccfa752185c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
93 schema:name Amino Acid Sequence
94 rdf:type schema:DefinedTerm
95 N1c347748e1ec4aa69f9ea3d183022fe5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
96 schema:name Cysteine Proteinase Inhibitors
97 rdf:type schema:DefinedTerm
98 N2391d395dc504888992e0864724eba72 schema:name doi
99 schema:value 10.1038/nchembio.178
100 rdf:type schema:PropertyValue
101 N2d0739799e814b4aaa7b405bfcdcd389 schema:name dimensions_id
102 schema:value pub.1028617423
103 rdf:type schema:PropertyValue
104 N30ca6649f4e3442fa208affdd5477621 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
105 schema:name Cholera Toxin
106 rdf:type schema:DefinedTerm
107 N3374e8b87bf649eba35b6ce89955a6b3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
108 schema:name Vibrio cholerae
109 rdf:type schema:DefinedTerm
110 N3647cbb3035a4b08b3c81fe377a6ff72 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
111 schema:name Crystallography, X-Ray
112 rdf:type schema:DefinedTerm
113 N42fb3aabe0f44589a062ac5c552a108c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name Cysteine Proteases
115 rdf:type schema:DefinedTerm
116 N4bdbe89209e947ccbec387f72f7116be schema:volumeNumber 5
117 rdf:type schema:PublicationVolume
118 N4c638d6d6a4646ec9ae09cdae99cd781 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Models, Molecular
120 rdf:type schema:DefinedTerm
121 N5074437ba8ff4661aad0c8e7756f2608 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
122 schema:name Spectroscopy, Fourier Transform Infrared
123 rdf:type schema:DefinedTerm
124 N6c91740cafbb4bc49c618bf786d27c22 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
125 schema:familyName Guzzetta
126 schema:givenName Andrew
127 rdf:type schema:Person
128 N7463c1d6cf7846d5b7bbfcdad4f28bbe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
129 schema:name Catalytic Domain
130 rdf:type schema:DefinedTerm
131 N77c41419bfc84d8bad10ab356c221383 rdf:first sg:person.0711630252.53
132 rdf:rest N971acdbba52c4f0cbda1b1ea19b875c2
133 N81d950a9777e4b03ba6f08d637181af1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Blotting, Western
135 rdf:type schema:DefinedTerm
136 N826d9e889bd0415ea875cf47a7ebd740 schema:issueNumber 7
137 rdf:type schema:PublicationIssue
138 N84d1b2f2929c4d30aa7ecccd8262235e rdf:first sg:person.0633741155.40
139 rdf:rest Nbd43eeb3b66942ff8c01933c79a91bcc
140 N928588be187d4166a8c8d0159ea93b2e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Enzyme Activation
142 rdf:type schema:DefinedTerm
143 N93df736fedb84cb48ec479db1244b0df rdf:first sg:person.07456715137.22
144 rdf:rest rdf:nil
145 N96ce6953745b470899b3874caf970ddb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Substrate Specificity
147 rdf:type schema:DefinedTerm
148 N971acdbba52c4f0cbda1b1ea19b875c2 rdf:first N6c91740cafbb4bc49c618bf786d27c22
149 rdf:rest Nd831fc630ac547fdaf5af3e7fb0aa3d9
150 Na425718eb1b149fca03a8e14ed9209a9 schema:name pubmed_id
151 schema:value 19465933
152 rdf:type schema:PropertyValue
153 Na884f0978a6747088cee33c27c68b69b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Molecular Sequence Data
155 rdf:type schema:DefinedTerm
156 Naab9512239c54aa5a97cd26c0e56912b rdf:first sg:person.0605144355.92
157 rdf:rest N93df736fedb84cb48ec479db1244b0df
158 Naaf7835af8e54daeb52074c70895f37b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
159 schema:name Protein Binding
160 rdf:type schema:DefinedTerm
161 Nbd43eeb3b66942ff8c01933c79a91bcc rdf:first sg:person.01214322055.04
162 rdf:rest N77c41419bfc84d8bad10ab356c221383
163 Ncbbcc0acbfb244fba5f4f1ee55b352ae schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Protein Structure, Secondary
165 rdf:type schema:DefinedTerm
166 Nd831fc630ac547fdaf5af3e7fb0aa3d9 rdf:first sg:person.01016560766.59
167 rdf:rest Naab9512239c54aa5a97cd26c0e56912b
168 Ndc9249f4df3a419e95576be80bdda045 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
169 schema:name Sequence Alignment
170 rdf:type schema:DefinedTerm
171 Ndf482073f42a4cfaa51e80336846e89a schema:name Springer Nature - SN SciGraph project
172 rdf:type schema:Organization
173 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
174 schema:name Biological Sciences
175 rdf:type schema:DefinedTerm
176 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
177 schema:name Biochemistry and Cell Biology
178 rdf:type schema:DefinedTerm
179 sg:grant.2501621 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.178
180 rdf:type schema:MonetaryGrant
181 sg:grant.2699532 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.178
182 rdf:type schema:MonetaryGrant
183 sg:journal.1327431 schema:issn 1552-4450
184 1552-4469
185 schema:name Nature Chemical Biology
186 rdf:type schema:Periodical
187 sg:person.01016560766.59 schema:affiliation https://www.grid.ac/institutes/grid.213917.f
188 schema:familyName Powers
189 schema:givenName James C
190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016560766.59
191 rdf:type schema:Person
192 sg:person.01214322055.04 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
193 schema:familyName Lupardus
194 schema:givenName Patrick J
195 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214322055.04
196 rdf:type schema:Person
197 sg:person.0605144355.92 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
198 schema:familyName Garcia
199 schema:givenName K Christopher
200 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605144355.92
201 rdf:type schema:Person
202 sg:person.0633741155.40 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
203 schema:familyName Shen
204 schema:givenName Aimee
205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633741155.40
206 rdf:type schema:Person
207 sg:person.0711630252.53 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
208 schema:familyName Albrow
209 schema:givenName Victoria E
210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0711630252.53
211 rdf:type schema:Person
212 sg:person.07456715137.22 schema:affiliation https://www.grid.ac/institutes/grid.168010.e
213 schema:familyName Bogyo
214 schema:givenName Matthew
215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07456715137.22
216 rdf:type schema:Person
217 sg:pub.10.1007/978-3-642-59605-6_4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014832933
218 https://doi.org/10.1007/978-3-642-59605-6_4
219 rdf:type schema:CreativeWork
220 sg:pub.10.1038/nature05622 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008166667
221 https://doi.org/10.1038/nature05622
222 rdf:type schema:CreativeWork
223 sg:pub.10.1038/nbt1408 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041621508
224 https://doi.org/10.1038/nbt1408
225 rdf:type schema:CreativeWork
226 sg:pub.10.1038/nchembio.70 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044068305
227 https://doi.org/10.1038/nchembio.70
228 rdf:type schema:CreativeWork
229 sg:pub.10.1038/nchembio707 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016969866
230 https://doi.org/10.1038/nchembio707
231 rdf:type schema:CreativeWork
232 https://app.dimensions.ai/details/publication/pub.1077413995 schema:CreativeWork
233 https://app.dimensions.ai/details/publication/pub.1082745710 schema:CreativeWork
234 https://doi.org/10.1016/j.micinf.2004.03.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042870090
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1021/bi060364p schema:sameAs https://app.dimensions.ai/details/publication/pub.1055201845
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1021/cr010182v schema:sameAs https://app.dimensions.ai/details/publication/pub.1009807257
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1021/jm025581c schema:sameAs https://app.dimensions.ai/details/publication/pub.1055947825
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1038/sj.emboj.7601700 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009667657
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1042/0264-6021:3500563 schema:sameAs https://app.dimensions.ai/details/publication/pub.1056714963
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1042/bj3500563 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020851826
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1073/pnas.0401104101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016250027
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1074/jbc.m703062200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047896444
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1074/jbc.m803334200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010981441
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1089/dna.2008.0737 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059252259
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1093/emboj/18.20.5453 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005207646
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1093/nar/gkm216 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052481822
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1099/jmm.0.47742-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060393590
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1107/s0021889807021206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012753217
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1107/s0907444903008126 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031860267
265 rdf:type schema:CreativeWork
266 https://doi.org/10.1107/s0907444904019158 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020281098
267 rdf:type schema:CreativeWork
268 https://doi.org/10.1107/s0907444996012255 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020405374
269 rdf:type schema:CreativeWork
270 https://doi.org/10.1107/s0907444998003254 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019779527
271 rdf:type schema:CreativeWork
272 https://doi.org/10.1111/j.1462-5822.2006.00876.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1016651505
273 rdf:type schema:CreativeWork
274 https://doi.org/10.1126/science.1162403 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062458569
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1128/iai.00045-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041728681
277 rdf:type schema:CreativeWork
278 https://doi.org/10.1128/iai.00506-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040079016
279 rdf:type schema:CreativeWork
280 https://doi.org/10.1128/iai.00508-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013536332
281 rdf:type schema:CreativeWork
282 https://doi.org/10.1128/iai.00525-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017607791
283 rdf:type schema:CreativeWork
284 https://doi.org/10.1128/iai.01308-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045818820
285 rdf:type schema:CreativeWork
286 https://doi.org/10.1128/iai.01503-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018047230
287 rdf:type schema:CreativeWork
288 https://doi.org/10.1128/jcm.00349-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010971298
289 rdf:type schema:CreativeWork
290 https://doi.org/10.1515/bc.2001.088 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019407825
291 rdf:type schema:CreativeWork
292 https://doi.org/10.1515/bchm.2001.382.5.727 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050575154
293 rdf:type schema:CreativeWork
294 https://www.grid.ac/institutes/grid.168010.e schema:alternateName Stanford University
295 schema:name Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA.
296 Department of Pathology and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, USA.
297 rdf:type schema:Organization
298 https://www.grid.ac/institutes/grid.213917.f schema:alternateName Georgia Institute of Technology
299 schema:name Department of Chemistry, Georgia Institute of Technology, Atlanta, Georgia, USA.
300 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...