DOI: 10.1126/science.7809628. Cleavage of an Amide Bond by a Ribozyme

10.1126/science.7809628

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

A variant form of a group I ribozyme, optimized by in vitro evolution for its ability to catalyze magnesium-dependent phosphoester transfer reactions involving DNA substrates, also catalyzes the cleavage of an unactivated alkyl amide when that linkage is presented in the context of an oligodeoxynucleotide analog. Substrates containing an amide bond that joins either two DNA oligos, or a DNA oligo and a short peptide, are cleaved in a magnesium-dependent fashion to generate the expected products. The first-order rate constant, k cat , is 0.1 × 10 -5 min -1 to 1 × 10 -5 min -1 for the DNA-flanked substrates, which corresponds to a rate acceleration of more than 10 3 as compared with the uncatalyzed reaction.

Bibliography

Dai, X., De Mesmaeker, A., & Joyce, G. F. (1995). Cleavage of an Amide Bond by a Ribozyme. Science, 267(5195), 237â240.

Authors 3

Xiaochang Dai (first)
Alain De Mesmaeker (additional)
Gerald F. Joyce (additional)

References 35 Referenced 95

BEAUCAGE, S.L., DEOXYNUCLEOSIDE PHOSPHORAMIDITES - A NEW CLASS OF KEY INTERMEDIATES FOR DEOXYPOLYNUCLEOTIDE SYNTHESIS, TETRAHEDRON LETTERS 22: 1859 (1981). (10.1016/S0040-4039(01)90461-7) / TETRAHEDRON LETTERS (1981)
10.1126/science.1496376
10.1126/science.2251500
10.1073/pnas.86.18.7054
BEVILACQUA, P.C., COMPARISON OF BINDING OF MIXED RIBOSE DEOXYRIBOSE ANALOGS OF CUCU TO A RIBOZYME AND TO GGAGAA BY EQUILIBRIUM DIALYSIS - EVIDENCE FOR RIBOZYME SPECIFIC INTERACTIONS WITH 2' OH GROUPS, BIOCHEMISTRY 30: 10632 (1991). (10.1021/bi00108a005) / BIOCHEMISTRY (1991)
BREAKER, R.R., INVENTING AND IMPROVING RIBOZYME FUNCTION - RATIONAL DESIGN VERSUS ITERATIVE SELECTION METHODS, TRENDS IN BIOTECHNOLOGY 12: 268 (1994). / TRENDS IN BIOTECHNOLOGY (1994)
CECH, T.R., RNA CATALYSIS BY A GROUP-I RIBOZYME - DEVELOPING A MODEL FOR TRANSITION-STATE STABILIZATION, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 17479 (1992). (10.1016/S0021-9258(19)37064-4) / JOURNAL OF BIOLOGICAL CHEMISTRY (1992)
CHAPMAN, K.B., IN-VITRO SELECTION OF CATALYTIC RNAS, CURRENT OPINION IN STRUCTURAL BIOLOGY 4: 618 (1994). (10.1016/S0959-440X(94)90227-5) / CURRENT OPINION IN STRUCTURAL BIOLOGY (1994)
EHLER, K.W., N,N'-CARBONYLDIIMIDAZOLE-INDUCED PEPTIDE FORMATION IN AQUEOUS-SOLUTION, BIOCHIMICA ET BIOPHYSICA ACTA 434: 233 (1976). (10.1016/0005-2795(76)90055-6) / BIOCHIMICA ET BIOPHYSICA ACTA (1976)
10.1038/319618a0
10.1016/0092-8674(83)90117-4
HERSCHLAG, D, CONTRIBUTIONS OF 2'-HYDROXYL GROUPS OF THE RNA SUBSTRATE TO BINDING AND CATALYSIS BY THE TETRAHYMENA RIBOZYME - AN ENERGETIC PICTURE OF AN ACTIVE-SITE COMPOSED OF RNA, BIOCHEMISTRY 32: 8299 (1993). (10.1021/bi00083a034) / BIOCHEMISTRY (1993)
10.1038/344405a0
10.1126/science.2922606
JOYCE, G.F., IN-VITRO EVOLUTION OF NUCLEIC-ACIDS, CURRENT OPINION IN STRUCTURAL BIOLOGY 4: 331 (1994). (10.1016/S0959-440X(94)90100-7) / CURRENT OPINION IN STRUCTURAL BIOLOGY (1994)
10.1038/338217a0
KAHNE, D, HYDROLYSIS OF A PEPTIDE-BOND IN NEUTRAL WATER, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 110: 7529 (1988). (10.1021/ja00230a041) / JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (1988)
10.1016/0092-8674(82)90414-7
LEBRETON, J, SYNTHESIS OF THYMIDINE DIMER DERIVATIVES CONTAINING AN AMIDE LINKAGE AND THEIR INCORPORATION INTO OLIGODEOXYRIBONUCLEOTIDES, TETRAHEDRON LETTERS 34: 6383 (1993). (10.1016/0040-4039(93)85051-W) / TETRAHEDRON LETTERS (1993)
MARTIN, M.T., ANTIBODY-CATALYZED HYDROLYSIS OF AN UNSUBSTITUTED AMIDE, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 116: 6508 (1994). (10.1021/ja00094a003) / JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (1994)
NOLLER, H.F., RIBOSOMES - DRUGS AND THE RNA WORLD, NATURE 353: 302 (1991). (10.1038/353302a0) / NATURE (1991)
10.1126/science.1604315
10.1038/361085a0
10.1126/science.1604316
10.1126/science.8009223
PYLE, A.M., RIBOZYME RECOGNITION OF RNA BY TERTIARY INTERACTIONS WITH SPECIFIC RIBOSE 2'-OH GROUPS, NATURE 350: 628 (1991). (10.1038/350628a0) / NATURE (1991)
PYLE, A.M., RNA SUBSTRATE BINDING-SITE IN THE CATALYTIC CORE OF THE TETRAHYMENA RIBOZYME, NATURE 358: 123 (1992). (10.1038/358123a0) / NATURE (1992)
RAILLARD S.A. unpublished data.
STEITZ, T.A., A GENERAL 2-METAL-ION MECHANISM FOR CATALYTIC RNA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 6498 (1993). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1993)
TSANG, J, EVOLUTIONARY OPTIMIZATION OF THE CATALYTIC PROPERTIES OF A DNA-CLEAVING RIBOZYME, BIOCHEMISTRY 33: 5966 (1994). (10.1021/bi00185a038) / BIOCHEMISTRY (1994)
TSANG J unpublished data.
10.1073/pnas.84.21.7383
YAMANA, T, STUDIES ON STABILITY OF AMIDES .1. HYDROLYSIS MECHANISM OF N-SUBSTITUTED ALIPHATIC AMIDES, CHEMICAL & PHARMACEUTICAL BULLETIN 20: 881 (1972). (10.1248/cpb.20.881) / CHEMICAL & PHARMACEUTICAL BULLETIN (1972)
10.1038/324429a0
ZIEBOLL, G, THE USE OF GEL-ELECTROPHORESIS TO STUDY THE REACTIONS OF ACTIVATED AMINO-ACIDS WITH OLIGONUCLEOTIDES, JOURNAL OF MOLECULAR EVOLUTION 38: 561 (1994). / JOURNAL OF MOLECULAR EVOLUTION (1994)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 27, 2006, 2:19 p.m.)
Deposited	1 year, 7 months ago (Jan. 14, 2024, 10:57 p.m.)
Indexed	1 month, 4 weeks ago (July 1, 2025, 6:30 a.m.)
Issued	30 years, 7 months ago (Jan. 13, 1995)
Published	30 years, 7 months ago (Jan. 13, 1995)
Published Print	30 years, 7 months ago (Jan. 13, 1995)

Funders 0

None

BibTeX

@article{Dai_1995, title={Cleavage of an Amide Bond by a Ribozyme}, volume={267}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7809628}, DOI={10.1126/science.7809628}, number={5195}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Dai, Xiaochang and De Mesmaeker, Alain and Joyce, Gerald F.}, year={1995}, month=jan, pages={237–240} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        1
      ]
    ],
    "date-time": "2025-07-01T10:30:32Z",
    "timestamp": 1751365832354
  },
  "reference-count": 35,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5195",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1995,
        1,
        13
      ]
    ]
  },
  "abstract": "<jats:p>\n            A variant form of a group I ribozyme, optimized by in vitro evolution for its ability to catalyze magnesium-dependent phosphoester transfer reactions involving DNA substrates, also catalyzes the cleavage of an unactivated alkyl amide when that linkage is presented in the context of an oligodeoxynucleotide analog. Substrates containing an amide bond that joins either two DNA oligos, or a DNA oligo and a short peptide, are cleaved in a magnesium-dependent fashion to generate the expected products. The first-order rate constant, k\n            <jats:sub>cat</jats:sub>\n            , is 0.1 \u00d7 10\n            <jats:sup>-5</jats:sup>\n            min\n            <jats:sup>-1</jats:sup>\n            to 1 \u00d7 10\n            <jats:sup>-5</jats:sup>\n            min\n            <jats:sup>-1</jats:sup>\n            for the DNA-flanked substrates, which corresponds to a rate acceleration of more than 10\n            <jats:sup>3</jats:sup>\n            as compared with the uncatalyzed reaction.\n          </jats:p>",
  "DOI": "10.1126/science.7809628",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        10,
        27
      ]
    ],
    "date-time": "2006-10-27T18:19:42Z",
    "timestamp": 1161973182000
  },
  "page": "237-240",
  "source": "Crossref",
  "is-referenced-by-count": 95,
  "title": "Cleavage of an Amide Bond by a Ribozyme",
  "prefix": "10.1126",
  "volume": "267",
  "author": [
    {
      "given": "Xiaochang",
      "family": "Dai",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA."
        }
      ]
    },
    {
      "given": "Alain",
      "family": "De Mesmaeker",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Central Research Laboratories, Ciba- Geigy Limited, Basel, Switzerland."
        }
      ]
    },
    {
      "given": "Gerald F.",
      "family": "Joyce",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_2_1_1_1",
      "doi-asserted-by": "crossref",
      "first-page": "1859",
      "DOI": "10.1016/S0040-4039(01)90461-7",
      "volume": "22",
      "year": "1981",
      "unstructured": "BEAUCAGE, S.L., DEOXYNUCLEOSIDE PHOSPHORAMIDITES - A NEW CLASS OF KEY INTERMEDIATES FOR DEOXYPOLYNUCLEOTIDE SYNTHESIS, TETRAHEDRON LETTERS 22: 1859 (1981).",
      "journal-title": "TETRAHEDRON LETTERS"
    },
    {
      "key": "e_1_2_1_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1496376"
    },
    {
      "key": "e_1_2_1_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2251500"
    },
    {
      "key": "e_1_2_1_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.86.18.7054"
    },
    {
      "key": "e_1_2_1_5_1",
      "doi-asserted-by": "crossref",
      "first-page": "10632",
      "DOI": "10.1021/bi00108a005",
      "volume": "30",
      "year": "1991",
      "unstructured": "BEVILACQUA, P.C., COMPARISON OF BINDING OF MIXED RIBOSE DEOXYRIBOSE ANALOGS OF CUCU TO A RIBOZYME AND TO GGAGAA BY EQUILIBRIUM DIALYSIS - EVIDENCE FOR RIBOZYME SPECIFIC INTERACTIONS WITH 2' OH GROUPS, BIOCHEMISTRY 30: 10632 (1991).",
      "journal-title": "BIOCHEMISTRY"
    },
    {
      "key": "e_1_2_1_6_1",
      "first-page": "268",
      "volume": "12",
      "year": "1994",
      "unstructured": "BREAKER, R.R., INVENTING AND IMPROVING RIBOZYME FUNCTION - RATIONAL DESIGN VERSUS ITERATIVE SELECTION METHODS, TRENDS IN BIOTECHNOLOGY 12: 268 (1994).",
      "journal-title": "TRENDS IN BIOTECHNOLOGY"
    },
    {
      "key": "e_1_2_1_7_1",
      "doi-asserted-by": "crossref",
      "first-page": "17479",
      "DOI": "10.1016/S0021-9258(19)37064-4",
      "volume": "267",
      "year": "1992",
      "unstructured": "CECH, T.R., RNA CATALYSIS BY A GROUP-I RIBOZYME - DEVELOPING A MODEL FOR TRANSITION-STATE STABILIZATION, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 17479 (1992).",
      "journal-title": "JOURNAL OF BIOLOGICAL CHEMISTRY"
    },
    {
      "key": "e_1_2_1_8_1",
      "doi-asserted-by": "crossref",
      "first-page": "618",
      "DOI": "10.1016/S0959-440X(94)90227-5",
      "volume": "4",
      "year": "1994",
      "unstructured": "CHAPMAN, K.B., IN-VITRO SELECTION OF CATALYTIC RNAS, CURRENT OPINION IN STRUCTURAL BIOLOGY 4: 618 (1994).",
      "journal-title": "CURRENT OPINION IN STRUCTURAL BIOLOGY"
    },
    {
      "key": "e_1_2_1_9_1",
      "doi-asserted-by": "crossref",
      "first-page": "233",
      "DOI": "10.1016/0005-2795(76)90055-6",
      "volume": "434",
      "year": "1976",
      "unstructured": "EHLER, K.W., N,N'-CARBONYLDIIMIDAZOLE-INDUCED PEPTIDE FORMATION IN AQUEOUS-SOLUTION, BIOCHIMICA ET BIOPHYSICA ACTA 434: 233 (1976).",
      "journal-title": "BIOCHIMICA ET BIOPHYSICA ACTA"
    },
    {
      "key": "e_1_2_1_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/319618a0"
    },
    {
      "key": "e_1_2_1_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(83)90117-4"
    },
    {
      "key": "e_1_2_1_12_1",
      "doi-asserted-by": "crossref",
      "first-page": "8299",
      "DOI": "10.1021/bi00083a034",
      "volume": "32",
      "year": "1993",
      "unstructured": "HERSCHLAG, D, CONTRIBUTIONS OF 2'-HYDROXYL GROUPS OF THE RNA SUBSTRATE TO BINDING AND CATALYSIS BY THE TETRAHYMENA RIBOZYME - AN ENERGETIC PICTURE OF AN ACTIVE-SITE COMPOSED OF RNA, BIOCHEMISTRY 32: 8299 (1993).",
      "journal-title": "BIOCHEMISTRY"
    },
    {
      "key": "e_1_2_1_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/344405a0"
    },
    {
      "key": "e_1_2_1_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2922606"
    },
    {
      "key": "e_1_2_1_15_1",
      "doi-asserted-by": "crossref",
      "first-page": "331",
      "DOI": "10.1016/S0959-440X(94)90100-7",
      "volume": "4",
      "year": "1994",
      "unstructured": "JOYCE, G.F., IN-VITRO EVOLUTION OF NUCLEIC-ACIDS, CURRENT OPINION IN STRUCTURAL BIOLOGY 4: 331 (1994).",
      "journal-title": "CURRENT OPINION IN STRUCTURAL BIOLOGY"
    },
    {
      "key": "e_1_2_1_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/338217a0"
    },
    {
      "key": "e_1_2_1_17_1",
      "doi-asserted-by": "crossref",
      "first-page": "7529",
      "DOI": "10.1021/ja00230a041",
      "volume": "110",
      "year": "1988",
      "unstructured": "KAHNE, D, HYDROLYSIS OF A PEPTIDE-BOND IN NEUTRAL WATER, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 110: 7529 (1988).",
      "journal-title": "JOURNAL OF THE AMERICAN CHEMICAL SOCIETY"
    },
    {
      "key": "e_1_2_1_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(82)90414-7"
    },
    {
      "key": "e_1_2_1_19_1",
      "doi-asserted-by": "crossref",
      "first-page": "6383",
      "DOI": "10.1016/0040-4039(93)85051-W",
      "volume": "34",
      "year": "1993",
      "unstructured": "LEBRETON, J, SYNTHESIS OF THYMIDINE DIMER DERIVATIVES CONTAINING AN AMIDE LINKAGE AND THEIR INCORPORATION INTO OLIGODEOXYRIBONUCLEOTIDES, TETRAHEDRON LETTERS 34: 6383 (1993).",
      "journal-title": "TETRAHEDRON LETTERS"
    },
    {
      "key": "e_1_2_1_20_1",
      "doi-asserted-by": "crossref",
      "first-page": "6508",
      "DOI": "10.1021/ja00094a003",
      "volume": "116",
      "year": "1994",
      "unstructured": "MARTIN, M.T., ANTIBODY-CATALYZED HYDROLYSIS OF AN UNSUBSTITUTED AMIDE, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 116: 6508 (1994).",
      "journal-title": "JOURNAL OF THE AMERICAN CHEMICAL SOCIETY"
    },
    {
      "key": "e_1_2_1_21_1",
      "doi-asserted-by": "crossref",
      "first-page": "302",
      "DOI": "10.1038/353302a0",
      "volume": "353",
      "year": "1991",
      "unstructured": "NOLLER, H.F., RIBOSOMES - DRUGS AND THE RNA WORLD, NATURE 353: 302 (1991).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1604315"
    },
    {
      "key": "e_1_2_1_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/361085a0"
    },
    {
      "key": "e_1_2_1_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1604316"
    },
    {
      "key": "e_1_2_1_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8009223"
    },
    {
      "key": "e_1_2_1_26_1",
      "doi-asserted-by": "crossref",
      "first-page": "628",
      "DOI": "10.1038/350628a0",
      "volume": "350",
      "year": "1991",
      "unstructured": "PYLE, A.M., RIBOZYME RECOGNITION OF RNA BY TERTIARY INTERACTIONS WITH SPECIFIC RIBOSE 2'-OH GROUPS, NATURE 350: 628 (1991).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_27_1",
      "doi-asserted-by": "crossref",
      "first-page": "123",
      "DOI": "10.1038/358123a0",
      "volume": "358",
      "year": "1992",
      "unstructured": "PYLE, A.M., RNA SUBSTRATE BINDING-SITE IN THE CATALYTIC CORE OF THE TETRAHYMENA RIBOZYME, NATURE 358: 123 (1992).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_28_1",
      "unstructured": "RAILLARD S.A. unpublished data."
    },
    {
      "key": "e_1_2_1_29_1",
      "first-page": "6498",
      "volume": "90",
      "year": "1993",
      "unstructured": "STEITZ, T.A., A GENERAL 2-METAL-ION MECHANISM FOR CATALYTIC RNA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 6498 (1993).",
      "journal-title": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"
    },
    {
      "key": "e_1_2_1_30_1",
      "doi-asserted-by": "crossref",
      "first-page": "5966",
      "DOI": "10.1021/bi00185a038",
      "volume": "33",
      "year": "1994",
      "unstructured": "TSANG, J, EVOLUTIONARY OPTIMIZATION OF THE CATALYTIC PROPERTIES OF A DNA-CLEAVING RIBOZYME, BIOCHEMISTRY 33: 5966 (1994).",
      "journal-title": "BIOCHEMISTRY"
    },
    {
      "key": "e_1_2_1_31_1",
      "unstructured": "TSANG J unpublished data."
    },
    {
      "key": "e_1_2_1_32_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.21.7383"
    },
    {
      "key": "e_1_2_1_33_1",
      "doi-asserted-by": "crossref",
      "first-page": "881",
      "DOI": "10.1248/cpb.20.881",
      "volume": "20",
      "year": "1972",
      "unstructured": "YAMANA, T, STUDIES ON STABILITY OF AMIDES .1. HYDROLYSIS MECHANISM OF N-SUBSTITUTED ALIPHATIC AMIDES, CHEMICAL & PHARMACEUTICAL BULLETIN 20: 881 (1972).",
      "journal-title": "CHEMICAL & PHARMACEUTICAL BULLETIN"
    },
    {
      "key": "e_1_2_1_34_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/324429a0"
    },
    {
      "key": "e_1_2_1_35_1",
      "first-page": "561",
      "volume": "38",
      "year": "1994",
      "unstructured": "ZIEBOLL, G, THE USE OF GEL-ELECTROPHORESIS TO STUDY THE REACTIONS OF ACTIVATED AMINO-ACIDS WITH OLIGONUCLEOTIDES, JOURNAL OF MOLECULAR EVOLUTION 38: 561 (1994).",
      "journal-title": "JOURNAL OF MOLECULAR EVOLUTION"
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.7809628",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        15
      ]
    ],
    "date-time": "2024-01-15T03:57:44Z",
    "timestamp": 1705291064000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.7809628"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1995,
        1,
        13
      ]
    ]
  },
  "references-count": 35,
  "journal-issue": {
    "issue": "5195",
    "published-print": {
      "date-parts": [
        [
          1995,
          1,
          13
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.7809628"
  ],
  "URL": "http://dx.doi.org/10.1126/science.7809628",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1995,
        1,
        13
      ]
    ]
  }
}