Synthesis in yeast of a functional oxidation-resistant mutant of human α1-antitrypsin View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1984-11

AUTHORS

Steven Rosenberg, Philip J. Barr, Richard C. Najarian, Robert A. Hallewell

ABSTRACT

Cumulative damage to lung tissue by leukocyte elastase is thought to be responsible for the development of pulmonary emphysema, an irreversible lung disease characterized by loss of lung elasticity. It is also thought to be involved in the rapidly developing and usually fatal adult respiratory distress syndrome. The primary defence against elastase damage is the anti-protease known as alpha 1-antitrypsin, a glycosylated serum protein of 394 amino acids. Oxidation of the methionine 358 residue located at the active centre of alpha 1-antitrypsin results in a dramatic decrease in inhibitory activity towards elastase which effectively inactivates the protective function. It has been suggested that this oxidation sensitivity has a regulatory function and allows tissue breakdown at sites of inflammation by inactivation of alpha 1-antitrypsin by oxygen radicals released by phagocytes. In the above diseases, however, the oxidative inactivation of alpha 1-antitrypsin is probably of major importance in allowing lung damage by elastase. An oxidation-resistant alpha 1-antitrypsin required for emphysemics and provide treatment for acute inflammatory respiratory conditions. To further the possibility of therapy for the above conditions, we describe here the synthesis in yeast of active, non-glycosylated, human alpha 1-antitrypsin. Site-directed mutagenesis has been used to construct an active, oxidation-resistant derivative containing a single methionine to valine substitution at the active centre. This demonstrates the potential of engineered modifications to protein molecules designed to improve their physiological function. More... »

PAGES

77-80

Journal

TITLE

Nature

ISSUE

5989

VOLUME

312

Related Patents

  • Alpha-1-Antitrypsin Mutants And Dna Coding Therefor And The Production Of Each, And Therapeutic Formulations Using Such Mutants And Their Preparation
  • Recombinant Methods For Production Of Serine Protease Inhibitors And Dna Sequences
  • Peptide Plasminogen Activators
  • Treatment Of Chronic Obstructive Pulmonary Disease By Low Dose Inhalation Of Protease Inhibitor
  • Peptide Plasminogen Activators
  • Thermostable Alpha1-Antitrypsin Mutein With A Disulfide Bond And The Method For Preparing It
  • Site Specific Mutagenesis In Alpha-1-Antitrypsin
  • Oxidation Resistant Il-2 Muteins And Their Production, Formulations Containing Such Muteins, And Dna Sequences And Expression Vectors Coding For Such Muteins And Corresponding Transformed Host Cells
  • Serine Protease Inhibitor Proteins, Medicaments Containing Them, Dna Sequences Coding For These Proteins And Methods For Producing These Proteins, Medicaments And Dna Sequences
  • Hcv Genomic Sequences For Diagnostics And Therapeutics
  • Peptide Plasminogen Activators
  • Modified Target Enzymes Having Catalytic Triads And Uses Thereof
  • Active Site Modified Protease Alpha-1-Antitrypsin Inhibitors And Their Production
  • Serine Protease Inhibitors And Methods For Isolation Of Same.
  • Alpha-1-Antitrypsin Mutants And Dna Coding Therefor And The Production Of Each, And Therapeutic Formulations Using Such Mutants And Their Preparation
  • Serine Protease Inhibitor Proteins, Medicaments Containing Them, Dna Sequences Coding For These Proteins And Methods For Producing These Proteins, Medicaments And Dna Sequences
  • Gene Expression Technique
  • Antibodies With Altered Effector Functions
  • Serine Protease Inhibitors And Methods For Isolation Of Same.
  • Active Site Modified Protease Alpha-1-Antitrypsin Inhibitors And Their Production
  • Dna Encoding Antibodies With Altered Effector Functions
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/312077a0

    DOI

    http://dx.doi.org/10.1038/312077a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1024320128

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/6387509


    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/2008/1102", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Cardiorespiratory Medicine and Haematology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acid Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Base Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cloning, Molecular", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Weight", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Oxidation-Reduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Plasmids", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Saccharomyces cerevisiae", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "alpha 1-Antitrypsin", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "familyName": "Rosenberg", 
            "givenName": "Steven", 
            "id": "sg:person.01126604136.61", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01126604136.61"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Barr", 
            "givenName": "Philip J.", 
            "id": "sg:person.01232072324.48", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01232072324.48"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Najarian", 
            "givenName": "Richard C.", 
            "id": "sg:person.01255356365.01", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255356365.01"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Hallewell", 
            "givenName": "Robert A.", 
            "id": "sg:person.01306506574.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01306506574.09"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1073/pnas.78.11.6613", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002108743"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/282471a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004324129", 
              "https://doi.org/10.1038/282471a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/282471a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004324129", 
              "https://doi.org/10.1038/282471a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/298347a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004599863", 
              "https://doi.org/10.1038/298347a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/275104a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006573233", 
              "https://doi.org/10.1038/275104a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/275104a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006573233", 
              "https://doi.org/10.1038/275104a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/227680a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010419937", 
              "https://doi.org/10.1038/227680a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.76.9.4350", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011704795"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.81.2.367", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016806845"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0076-6879(83)01005-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020426990"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0022-2836(69)90288-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023146115"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.0954-6820.1964.tb00567.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023252801"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.0954-6820.1964.tb00567.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023252801"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.74.12.5463", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025360556"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0003-2697(76)90527-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025529346"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/9.13.2989", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027178214"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.78.11.6826", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031444483"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.78.1.435", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032474339"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0091-679x(08)60951-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032976738"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.80.24.7461", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041457321"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/10.20.6487", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042771139"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0378-1119(77)90000-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044383550"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/297655a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044608056", 
              "https://doi.org/10.1038/297655a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.75.4.1929", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046556482"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1432-1033.1978.tb12078.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049575082"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/298329a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052618234", 
              "https://doi.org/10.1038/298329a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.81.15.4642", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053301653"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1080/00365516309051324", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053616315"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi00649a017", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055184003"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1089/dna.1983.2.255", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1059250720"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.316188", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062595583"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.377496", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062621416"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.6356360", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062636909"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/j.1460-2075.1987.tb04807.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1079517151"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079566473", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079939791", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1081599958", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1081608740", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082086212", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082100001", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1984-11", 
        "datePublishedReg": "1984-11-01", 
        "description": "Cumulative damage to lung tissue by leukocyte elastase is thought to be responsible for the development of pulmonary emphysema, an irreversible lung disease characterized by loss of lung elasticity. It is also thought to be involved in the rapidly developing and usually fatal adult respiratory distress syndrome. The primary defence against elastase damage is the anti-protease known as alpha 1-antitrypsin, a glycosylated serum protein of 394 amino acids. Oxidation of the methionine 358 residue located at the active centre of alpha 1-antitrypsin results in a dramatic decrease in inhibitory activity towards elastase which effectively inactivates the protective function. It has been suggested that this oxidation sensitivity has a regulatory function and allows tissue breakdown at sites of inflammation by inactivation of alpha 1-antitrypsin by oxygen radicals released by phagocytes. In the above diseases, however, the oxidative inactivation of alpha 1-antitrypsin is probably of major importance in allowing lung damage by elastase. An oxidation-resistant alpha 1-antitrypsin required for emphysemics and provide treatment for acute inflammatory respiratory conditions. To further the possibility of therapy for the above conditions, we describe here the synthesis in yeast of active, non-glycosylated, human alpha 1-antitrypsin. Site-directed mutagenesis has been used to construct an active, oxidation-resistant derivative containing a single methionine to valine substitution at the active centre. This demonstrates the potential of engineered modifications to protein molecules designed to improve their physiological function.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/312077a0", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0090-0028", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "5989", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "312"
          }
        ], 
        "name": "Synthesis in yeast of a functional oxidation-resistant mutant of human \u03b11-antitrypsin", 
        "pagination": "77-80", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "73dd4248cc485eebfd71f81ab7abc467f72c11fbfc6d3d07c0b9dc93f4b2f1d7"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "6387509"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0410462"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/312077a0"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1024320128"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/312077a0", 
          "https://app.dimensions.ai/details/publication/pub.1024320128"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T18:56", 
        "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/v90/0000000001_0000000264/records_8678_00000424.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/articles/312077a0"
      }
    ]
     

    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.10.1038/312077a0'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/312077a0'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/312077a0'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/312077a0'


     

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

    242 TRIPLES      21 PREDICATES      78 URIs      33 LITERALS      21 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/312077a0 schema:about N1581cd3f71664106ae0c0dcb95778867
    2 N1dd2a1d8f1344664a7ce3b18806f1736
    3 N21832b52e5f24437a2b8e9c51bd76be6
    4 N3ee13e96f73a47188266e25680d903db
    5 N4cd2228197c044e89bf6b0098e7ccc53
    6 N4cd88861a6c44b79a6bc26c12f9d9c42
    7 N85435e9bfc27432781d0025e1f85f210
    8 Na5c53e7383e544ed83e236b7f080a673
    9 Nb416681fcd224fbdb901c69ef2832cc3
    10 Nb4b650dca98d4f88a5975c4d1524203a
    11 Nc3b0b90398ff44069a11addebd433db6
    12 Nf38a08f9c03a40e8893697c474f08bb4
    13 anzsrc-for:11
    14 anzsrc-for:1102
    15 schema:author N0483603b10bd44da882794b302efd595
    16 schema:citation sg:pub.10.1038/227680a0
    17 sg:pub.10.1038/275104a0
    18 sg:pub.10.1038/282471a0
    19 sg:pub.10.1038/297655a0
    20 sg:pub.10.1038/298329a0
    21 sg:pub.10.1038/298347a0
    22 https://app.dimensions.ai/details/publication/pub.1079566473
    23 https://app.dimensions.ai/details/publication/pub.1079939791
    24 https://app.dimensions.ai/details/publication/pub.1081599958
    25 https://app.dimensions.ai/details/publication/pub.1081608740
    26 https://app.dimensions.ai/details/publication/pub.1082086212
    27 https://app.dimensions.ai/details/publication/pub.1082100001
    28 https://doi.org/10.1002/j.1460-2075.1987.tb04807.x
    29 https://doi.org/10.1016/0003-2697(76)90527-3
    30 https://doi.org/10.1016/0022-2836(69)90288-5
    31 https://doi.org/10.1016/0076-6879(83)01005-8
    32 https://doi.org/10.1016/0378-1119(77)90000-2
    33 https://doi.org/10.1016/s0091-679x(08)60951-6
    34 https://doi.org/10.1021/bi00649a017
    35 https://doi.org/10.1073/pnas.74.12.5463
    36 https://doi.org/10.1073/pnas.75.4.1929
    37 https://doi.org/10.1073/pnas.76.9.4350
    38 https://doi.org/10.1073/pnas.78.1.435
    39 https://doi.org/10.1073/pnas.78.11.6613
    40 https://doi.org/10.1073/pnas.78.11.6826
    41 https://doi.org/10.1073/pnas.80.24.7461
    42 https://doi.org/10.1073/pnas.81.15.4642
    43 https://doi.org/10.1073/pnas.81.2.367
    44 https://doi.org/10.1080/00365516309051324
    45 https://doi.org/10.1089/dna.1983.2.255
    46 https://doi.org/10.1093/nar/10.20.6487
    47 https://doi.org/10.1093/nar/9.13.2989
    48 https://doi.org/10.1111/j.0954-6820.1964.tb00567.x
    49 https://doi.org/10.1111/j.1432-1033.1978.tb12078.x
    50 https://doi.org/10.1126/science.316188
    51 https://doi.org/10.1126/science.377496
    52 https://doi.org/10.1126/science.6356360
    53 schema:datePublished 1984-11
    54 schema:datePublishedReg 1984-11-01
    55 schema:description Cumulative damage to lung tissue by leukocyte elastase is thought to be responsible for the development of pulmonary emphysema, an irreversible lung disease characterized by loss of lung elasticity. It is also thought to be involved in the rapidly developing and usually fatal adult respiratory distress syndrome. The primary defence against elastase damage is the anti-protease known as alpha 1-antitrypsin, a glycosylated serum protein of 394 amino acids. Oxidation of the methionine 358 residue located at the active centre of alpha 1-antitrypsin results in a dramatic decrease in inhibitory activity towards elastase which effectively inactivates the protective function. It has been suggested that this oxidation sensitivity has a regulatory function and allows tissue breakdown at sites of inflammation by inactivation of alpha 1-antitrypsin by oxygen radicals released by phagocytes. In the above diseases, however, the oxidative inactivation of alpha 1-antitrypsin is probably of major importance in allowing lung damage by elastase. An oxidation-resistant alpha 1-antitrypsin required for emphysemics and provide treatment for acute inflammatory respiratory conditions. To further the possibility of therapy for the above conditions, we describe here the synthesis in yeast of active, non-glycosylated, human alpha 1-antitrypsin. Site-directed mutagenesis has been used to construct an active, oxidation-resistant derivative containing a single methionine to valine substitution at the active centre. This demonstrates the potential of engineered modifications to protein molecules designed to improve their physiological function.
    56 schema:genre research_article
    57 schema:inLanguage en
    58 schema:isAccessibleForFree false
    59 schema:isPartOf N85b5445be2b74479b16fc87e82a14d02
    60 Nac1bf69975644505ba0a6911cba00d9c
    61 sg:journal.1018957
    62 schema:name Synthesis in yeast of a functional oxidation-resistant mutant of human α1-antitrypsin
    63 schema:pagination 77-80
    64 schema:productId N28957cb9acdc4a8bb4cf1874651764bf
    65 N4e3d371deb6244fe817a08885c4b4eae
    66 N8dd5476ee22b4dfdb7b661e260e483ea
    67 N8fe3e868c6024a6db583539f6f51fecb
    68 N99a48615737e498f8784685907e6a4b5
    69 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024320128
    70 https://doi.org/10.1038/312077a0
    71 schema:sdDatePublished 2019-04-10T18:56
    72 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    73 schema:sdPublisher N5f1207c1697941fdab1b1a805811d447
    74 schema:url http://www.nature.com/articles/312077a0
    75 sgo:license sg:explorer/license/
    76 sgo:sdDataset articles
    77 rdf:type schema:ScholarlyArticle
    78 N0483603b10bd44da882794b302efd595 rdf:first sg:person.01126604136.61
    79 rdf:rest N8618bf23ed584ef2a952117c377ac29b
    80 N1581cd3f71664106ae0c0dcb95778867 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    81 schema:name DNA
    82 rdf:type schema:DefinedTerm
    83 N1d522859f61b48f5b8f5b0a1a2c1dd82 rdf:first sg:person.01306506574.09
    84 rdf:rest rdf:nil
    85 N1dd2a1d8f1344664a7ce3b18806f1736 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    86 schema:name Amino Acid Sequence
    87 rdf:type schema:DefinedTerm
    88 N21832b52e5f24437a2b8e9c51bd76be6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    89 schema:name alpha 1-Antitrypsin
    90 rdf:type schema:DefinedTerm
    91 N28957cb9acdc4a8bb4cf1874651764bf schema:name dimensions_id
    92 schema:value pub.1024320128
    93 rdf:type schema:PropertyValue
    94 N3ee13e96f73a47188266e25680d903db schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    95 schema:name Mutation
    96 rdf:type schema:DefinedTerm
    97 N4cd2228197c044e89bf6b0098e7ccc53 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    98 schema:name Base Sequence
    99 rdf:type schema:DefinedTerm
    100 N4cd88861a6c44b79a6bc26c12f9d9c42 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    101 schema:name Cloning, Molecular
    102 rdf:type schema:DefinedTerm
    103 N4e3d371deb6244fe817a08885c4b4eae schema:name readcube_id
    104 schema:value 73dd4248cc485eebfd71f81ab7abc467f72c11fbfc6d3d07c0b9dc93f4b2f1d7
    105 rdf:type schema:PropertyValue
    106 N5f1207c1697941fdab1b1a805811d447 schema:name Springer Nature - SN SciGraph project
    107 rdf:type schema:Organization
    108 N85435e9bfc27432781d0025e1f85f210 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    109 schema:name Oxidation-Reduction
    110 rdf:type schema:DefinedTerm
    111 N85b5445be2b74479b16fc87e82a14d02 schema:issueNumber 5989
    112 rdf:type schema:PublicationIssue
    113 N8618bf23ed584ef2a952117c377ac29b rdf:first sg:person.01232072324.48
    114 rdf:rest Ncdb6ade40dda4401a4b77ad96c4b3f03
    115 N8dd5476ee22b4dfdb7b661e260e483ea schema:name doi
    116 schema:value 10.1038/312077a0
    117 rdf:type schema:PropertyValue
    118 N8fe3e868c6024a6db583539f6f51fecb schema:name pubmed_id
    119 schema:value 6387509
    120 rdf:type schema:PropertyValue
    121 N99a48615737e498f8784685907e6a4b5 schema:name nlm_unique_id
    122 schema:value 0410462
    123 rdf:type schema:PropertyValue
    124 Na5c53e7383e544ed83e236b7f080a673 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    125 schema:name Humans
    126 rdf:type schema:DefinedTerm
    127 Nac1bf69975644505ba0a6911cba00d9c schema:volumeNumber 312
    128 rdf:type schema:PublicationVolume
    129 Nb416681fcd224fbdb901c69ef2832cc3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Molecular Weight
    131 rdf:type schema:DefinedTerm
    132 Nb4b650dca98d4f88a5975c4d1524203a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Genes
    134 rdf:type schema:DefinedTerm
    135 Nc3b0b90398ff44069a11addebd433db6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    136 schema:name Saccharomyces cerevisiae
    137 rdf:type schema:DefinedTerm
    138 Ncdb6ade40dda4401a4b77ad96c4b3f03 rdf:first sg:person.01255356365.01
    139 rdf:rest N1d522859f61b48f5b8f5b0a1a2c1dd82
    140 Nf38a08f9c03a40e8893697c474f08bb4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Plasmids
    142 rdf:type schema:DefinedTerm
    143 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    144 schema:name Medical and Health Sciences
    145 rdf:type schema:DefinedTerm
    146 anzsrc-for:1102 schema:inDefinedTermSet anzsrc-for:
    147 schema:name Cardiorespiratory Medicine and Haematology
    148 rdf:type schema:DefinedTerm
    149 sg:journal.1018957 schema:issn 0090-0028
    150 1476-4687
    151 schema:name Nature
    152 rdf:type schema:Periodical
    153 sg:person.01126604136.61 schema:familyName Rosenberg
    154 schema:givenName Steven
    155 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01126604136.61
    156 rdf:type schema:Person
    157 sg:person.01232072324.48 schema:familyName Barr
    158 schema:givenName Philip J.
    159 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01232072324.48
    160 rdf:type schema:Person
    161 sg:person.01255356365.01 schema:familyName Najarian
    162 schema:givenName Richard C.
    163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255356365.01
    164 rdf:type schema:Person
    165 sg:person.01306506574.09 schema:familyName Hallewell
    166 schema:givenName Robert A.
    167 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01306506574.09
    168 rdf:type schema:Person
    169 sg:pub.10.1038/227680a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010419937
    170 https://doi.org/10.1038/227680a0
    171 rdf:type schema:CreativeWork
    172 sg:pub.10.1038/275104a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006573233
    173 https://doi.org/10.1038/275104a0
    174 rdf:type schema:CreativeWork
    175 sg:pub.10.1038/282471a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004324129
    176 https://doi.org/10.1038/282471a0
    177 rdf:type schema:CreativeWork
    178 sg:pub.10.1038/297655a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044608056
    179 https://doi.org/10.1038/297655a0
    180 rdf:type schema:CreativeWork
    181 sg:pub.10.1038/298329a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052618234
    182 https://doi.org/10.1038/298329a0
    183 rdf:type schema:CreativeWork
    184 sg:pub.10.1038/298347a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004599863
    185 https://doi.org/10.1038/298347a0
    186 rdf:type schema:CreativeWork
    187 https://app.dimensions.ai/details/publication/pub.1079566473 schema:CreativeWork
    188 https://app.dimensions.ai/details/publication/pub.1079939791 schema:CreativeWork
    189 https://app.dimensions.ai/details/publication/pub.1081599958 schema:CreativeWork
    190 https://app.dimensions.ai/details/publication/pub.1081608740 schema:CreativeWork
    191 https://app.dimensions.ai/details/publication/pub.1082086212 schema:CreativeWork
    192 https://app.dimensions.ai/details/publication/pub.1082100001 schema:CreativeWork
    193 https://doi.org/10.1002/j.1460-2075.1987.tb04807.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1079517151
    194 rdf:type schema:CreativeWork
    195 https://doi.org/10.1016/0003-2697(76)90527-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025529346
    196 rdf:type schema:CreativeWork
    197 https://doi.org/10.1016/0022-2836(69)90288-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023146115
    198 rdf:type schema:CreativeWork
    199 https://doi.org/10.1016/0076-6879(83)01005-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020426990
    200 rdf:type schema:CreativeWork
    201 https://doi.org/10.1016/0378-1119(77)90000-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044383550
    202 rdf:type schema:CreativeWork
    203 https://doi.org/10.1016/s0091-679x(08)60951-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032976738
    204 rdf:type schema:CreativeWork
    205 https://doi.org/10.1021/bi00649a017 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055184003
    206 rdf:type schema:CreativeWork
    207 https://doi.org/10.1073/pnas.74.12.5463 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025360556
    208 rdf:type schema:CreativeWork
    209 https://doi.org/10.1073/pnas.75.4.1929 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046556482
    210 rdf:type schema:CreativeWork
    211 https://doi.org/10.1073/pnas.76.9.4350 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011704795
    212 rdf:type schema:CreativeWork
    213 https://doi.org/10.1073/pnas.78.1.435 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032474339
    214 rdf:type schema:CreativeWork
    215 https://doi.org/10.1073/pnas.78.11.6613 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002108743
    216 rdf:type schema:CreativeWork
    217 https://doi.org/10.1073/pnas.78.11.6826 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031444483
    218 rdf:type schema:CreativeWork
    219 https://doi.org/10.1073/pnas.80.24.7461 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041457321
    220 rdf:type schema:CreativeWork
    221 https://doi.org/10.1073/pnas.81.15.4642 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053301653
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1073/pnas.81.2.367 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016806845
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1080/00365516309051324 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053616315
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1089/dna.1983.2.255 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059250720
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1093/nar/10.20.6487 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042771139
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1093/nar/9.13.2989 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027178214
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1111/j.0954-6820.1964.tb00567.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1023252801
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1111/j.1432-1033.1978.tb12078.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1049575082
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.1126/science.316188 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062595583
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.1126/science.377496 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062621416
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.1126/science.6356360 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062636909
    242 rdf:type schema:CreativeWork
     




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


    ...