DOI: 10.1098/rsta.1986.0041. Structure and activity of the tyrosy1-tRNA synthetase: the hydrogen bond in catalysis and specificity

Structure and activity of the tyrosy1-tRNA synthetase: the hydrogen bond in catalysis and specificity

10.1098/rsta.1986.0041

Crossref journal-article

The Royal Society

Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences (175)

Abstract

The role ofhydrogen bonding in specificity, binding and catalysis by the tyrosyl-tRNA synthetase from Bacillus stearothermophilus has been investigated by systematic mutation of residues which form hydrogen bonds with substrates during the reaction between ATP and tyrosine to form tyrosyl adenylate. Data on hydrogen bonding as a determinant of biological specificity are summarized thus: deletion of an hydrogen-bond donor or acceptor between the enzyme and substrate to leave an unpaired but uncharged acceptor or donor weakens binding by only 2-7 kJ mol -1 ; but deletion to leave an unpaired but charged acceptor or donor weakens binding by some 17 kJ mol -1 or so. Hydrogen bonding is found to have a profound role in catalysis by mediating the differential binding of substrates, transition states and products. The formation of tyrosyl adenylate is not catalysed by classical mechanisms of acid-base or nucleophilic catalysis but the enhancement of rate is solely a result of a combination ofhydrogen bonding and electrostatic interactions which stabilize the transition state of the substrates relative to their ground states. The binding energy of ATP increases by more than 29 kJ mol -1 as it passes through the transition state, enhancing the rate by more than a factor of 10 5 . The residues involved in differential binding are spread over the molecule, away from the seat of reaction. The catalysis is delocalized over the whole binding site and not restricted to one or two specific residues. Some regions of the binding site are complementary in structure to the intermediate, tyrosyl adenylate. The apparent binding energies of certain side chains increase as the reaction proceeds, being weakest in the enzyme—substrate complex, stronger in the enzyme-transition-state complex and strongest in the enzyme-intermediate complex. This converts the unfavourable equilibrium constant for the formation of tyrosyl adenylate in solution to a favourable value for the enzyme-bound reagents and helps sequester the reactive tyrosyl adenylate.

Bibliography

Structure and activity of the tyrosy1-tRNA synthetase: the hydrogen bond in catalysis and specificity. (1986). Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences, 317(1540), 305â320.

Authors 0

None

References 30 Referenced 16

Barker D. G. & Winter G. 1982
{'key': 'p_2', 'first-page': '191', 'article-title': 'In Biological macromolecules and. pp. 442-469. New York: Wiley', 'volume': '145', 'author': 'Blow D. M.', 'year': '1985', 'journal-title': 'FEBSLett.'} / FEBSLett. / In Biological macromolecules and. pp. 442-469. New York: Wiley by Blow D. M. (1985)
Cantor C. R. & Schimmel P. R. 1980 Biophysical chemistry part 1 p. 277. New York: Freeman.
Carter P. J. Winter G. Wilkinson A. J. & Fersht A. R. 1984 Cell 38 835-840. (10.1016/0092-8674(84)90278-2)
{'key': 'p_5', 'first-page': '651', 'article-title': 'J. molec', 'volume': '159', 'author': 'Dessen P.', 'year': '1982', 'journal-title': 'Biol.'} / Biol. / J. molec by Dessen P. (1982)
10.1098/rspb.1974.0084
Fersht A. R. Ashford J. S. Bruton C. J. Jakes R. Koch G. L. W. & Hartley B. S. 1975a Biochemistry 14 1-4. (10.1021/bi00672a001)
Fersht A. R. Mulvey R. S. M. & Koch G. L. E. 1975 bBiochemistry 14 13-18. (10.1021/bi00672a003)
10.1002/anie.198404673
10.1038/314235a0
Fersht A. R. Wilkinson A. J. Carter P. & Winter G. 19856 Biochemistry 24 585-586.
{'key': 'p_12', 'first-page': '5766', 'article-title': 'J. Am. chem', 'volume': '94', 'author': 'Hine J.', 'year': '1972', 'journal-title': 'Soc.'} / Soc. / J. Am. chem by Hine J. (1972)
Jencks W. P. 1969 Catalysis in chemistry and enzymology pp. 321-322. New York: McGraw Hill.
{'key': 'p_14', 'first-page': '577', 'article-title': 'J. molec', 'volume': '105', 'author': 'Irwin M. J.', 'year': '1976', 'journal-title': 'Biol.'} / Biol. / J. molec by Irwin M. J. (1976)
10.1016/S0065-3233(08)60608-7
Klotz I. M. & Franzen J. S. 1962
{'key': 'p_17', 'first-page': '3461', 'article-title': 'Biochemistry 13, 2307-2312. J.Am. chem', 'volume': '84', 'author': 'Koch G. L. E.', 'year': '1974', 'journal-title': 'Soc.'} / Soc. / Biochemistry 13, 2307-2312. J.Am. chem by Koch G. L. E. (1974)
Leatherbarrow R. J. Fersht A. R. & Winter G. 1985 Proc. natn. Acad. Sci. U.S.A. (In the press.)
Lowe G. & Tansley G. 1984 Tetrahedron 40 113-117. (10.1016/0040-4020(84)85109-1)
{'key': 'p_20', 'first-page': '477', 'article-title': 'J. molec', 'volume': '173', 'author': 'Monteilhet C.', 'year': '1984', 'journal-title': 'Biol.'} / Biol. / J. molec by Monteilhet C. (1984)
Pauling L. 1946 Chem. Engng
{'key': 'p_22', 'first-page': '489', 'article-title': 'J. molec', 'volume': '145', 'author': 'Rubin J.', 'year': '1981', 'journal-title': 'Biol.'} / Biol. / J. molec by Rubin J. (1981)
Waye M. M. Y. Winter G. Wilkinson A. J. & Fersht A. R. 1983 EMBO J. 2 1827-1829. (10.1002/j.1460-2075.1983.tb01665.x)
Wilkinson A. J. Fersht A. R. Blow D. M. & Winter G. 1983 Biochemistry 22 3581-3586. (10.1021/bi00284a007)
10.1038/307187a0
{'key': 'p_26', 'first-page': '765', 'article-title': 'J.Am. chem', 'volume': '106', 'author': 'Weiner S. J.', 'year': '1984', 'journal-title': 'Soc.'} / Soc. / J.Am. chem by Weiner S. J. (1984)
10.1038/316656a0
Wells T. N. C. & Fersht A. R. 1986 Biochemistry. (In the press.)
10.1038/299756a0
{'key': 'p_30', 'first-page': '383', 'article-title': 'Eur', 'volume': '132', 'author': 'Winter G.', 'year': '1983', 'journal-title': 'J. Biochem.'} / J. Biochem. / Eur by Winter G. (1983)

Dates

Type	When
Created	18 years, 8 months ago (Dec. 15, 2006, 5:38 p.m.)
Deposited	4 years, 6 months ago (Feb. 20, 2021, 8:13 p.m.)
Indexed	2 days, 22 hours ago (Sept. 4, 2025, 9:17 a.m.)
Issued	39 years, 4 months ago (April 30, 1986)
Published	39 years, 4 months ago (April 30, 1986)
Published Online	28 years, 8 months ago (Jan. 1, 1997)
Published Print	39 years, 4 months ago (April 30, 1986)

Funders 0

None

BibTeX

@article{1986, volume={317}, ISSN={2054-0272}, url={http://dx.doi.org/10.1098/rsta.1986.0041}, DOI={10.1098/rsta.1986.0041}, number={1540}, journal={Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences}, publisher={The Royal Society}, year={1986}, month=apr, pages={305–320} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        4
      ]
    ],
    "date-time": "2025-09-04T13:17:16Z",
    "timestamp": 1756991836498
  },
  "reference-count": 30,
  "publisher": "The Royal Society",
  "issue": "1540",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            1986,
            4,
            30
          ]
        ],
        "date-time": "1986-04-30T00:00:00Z",
        "timestamp": 515203200000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://royalsociety.org/journals/ethics-policies/data-sharing-mining/"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1986,
        4,
        30
      ]
    ]
  },
  "abstract": "<jats:p>\n            The role ofhydrogen bonding in specificity, binding and catalysis by the tyrosyl-tRNA synthetase from\n            <jats:italic>Bacillus stearothermophilus</jats:italic>\n            has been investigated by systematic mutation of residues which form hydrogen bonds with substrates during the reaction between ATP and tyrosine to form tyrosyl adenylate. Data on hydrogen bonding as a determinant of biological specificity are summarized thus: deletion of an hydrogen-bond donor or acceptor between the enzyme and substrate to leave an unpaired but uncharged acceptor or donor weakens binding by only 2-7 kJ mol\n            <jats:sup>-1</jats:sup>\n            ; but deletion to leave an unpaired but charged acceptor or donor weakens binding by some 17 kJ mol\n            <jats:sup>-1</jats:sup>\n            or so. Hydrogen bonding is found to have a profound role in catalysis by mediating the differential binding of substrates, transition states and products. The formation of tyrosyl adenylate is not catalysed by classical mechanisms of acid-base or nucleophilic catalysis but the enhancement of rate is solely a result of a combination ofhydrogen bonding and electrostatic interactions which stabilize the transition state of the substrates relative to their ground states. The binding energy of ATP increases by more than 29 kJ mol\n            <jats:sup>-1</jats:sup>\n            as it passes through the transition state, enhancing the rate by more than a factor of 10\n            <jats:sup>5</jats:sup>\n            . The residues involved in differential binding are spread over the molecule, away from the seat of reaction. The catalysis is delocalized over the whole binding site and not restricted to one or two specific residues. Some regions of the binding site are complementary in structure to the intermediate, tyrosyl adenylate. The apparent binding energies of certain side chains increase as the reaction proceeds, being weakest in the enzyme\u2014substrate complex, stronger in the enzyme-transition-state complex and strongest in the enzyme-intermediate complex. This converts the unfavourable equilibrium constant for the formation of tyrosyl adenylate in solution to a favourable value for the enzyme-bound reagents and helps sequester the reactive tyrosyl adenylate.\n          </jats:p>",
  "DOI": "10.1098/rsta.1986.0041",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        12,
        15
      ]
    ],
    "date-time": "2006-12-15T22:38:29Z",
    "timestamp": 1166222309000
  },
  "page": "305-320",
  "source": "Crossref",
  "is-referenced-by-count": 16,
  "title": "Structure and activity of the tyrosy1-tRNA synthetase: the hydrogen bond in catalysis and specificity",
  "prefix": "10.1098",
  "volume": "317",
  "member": "175",
  "published-online": {
    "date-parts": [
      [
        1997,
        1
      ]
    ]
  },
  "reference": [
    {
      "key": "p_1",
      "unstructured": "Barker D. G. & Winter G. 1982"
    },
    {
      "key": "p_2",
      "first-page": "191",
      "article-title": "In Biological macromolecules and. pp. 442-469. New York: Wiley",
      "volume": "145",
      "author": "Blow D. M.",
      "year": "1985",
      "journal-title": "FEBSLett."
    },
    {
      "key": "p_3",
      "unstructured": "Cantor C. R. & Schimmel P. R. 1980 Biophysical chemistry part 1 p. 277. New York: Freeman."
    },
    {
      "key": "p_4",
      "doi-asserted-by": "crossref",
      "unstructured": "Carter P. J. Winter G. Wilkinson A. J. & Fersht A. R. 1984 Cell 38 835-840.",
      "DOI": "10.1016/0092-8674(84)90278-2"
    },
    {
      "key": "p_5",
      "first-page": "651",
      "article-title": "J. molec",
      "volume": "159",
      "author": "Dessen P.",
      "year": "1982",
      "journal-title": "Biol."
    },
    {
      "key": "p_6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1098/rspb.1974.0084"
    },
    {
      "key": "p_7",
      "doi-asserted-by": "crossref",
      "unstructured": "Fersht A. R. Ashford J. S. Bruton C. J. Jakes R. Koch G. L. W. & Hartley B. S. 1975a Biochemistry 14 1-4.",
      "DOI": "10.1021/bi00672a001"
    },
    {
      "key": "p_8",
      "doi-asserted-by": "crossref",
      "unstructured": "Fersht A. R. Mulvey R. S. M. & Koch G. L. E. 1975 bBiochemistry 14 13-18.",
      "DOI": "10.1021/bi00672a003"
    },
    {
      "key": "p_9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/anie.198404673"
    },
    {
      "key": "p_10",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/314235a0"
    },
    {
      "key": "p_11",
      "unstructured": "Fersht A. R. Wilkinson A. J. Carter P. & Winter G. 19856 Biochemistry 24 585-586."
    },
    {
      "key": "p_12",
      "first-page": "5766",
      "article-title": "J. Am. chem",
      "volume": "94",
      "author": "Hine J.",
      "year": "1972",
      "journal-title": "Soc."
    },
    {
      "key": "p_13",
      "unstructured": "Jencks W. P. 1969 Catalysis in chemistry and enzymology pp. 321-322. New York: McGraw Hill."
    },
    {
      "key": "p_14",
      "first-page": "577",
      "article-title": "J. molec",
      "volume": "105",
      "author": "Irwin M. J.",
      "year": "1976",
      "journal-title": "Biol."
    },
    {
      "key": "p_15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0065-3233(08)60608-7"
    },
    {
      "key": "p_16",
      "unstructured": "Klotz I. M. & Franzen J. S. 1962"
    },
    {
      "key": "p_17",
      "first-page": "3461",
      "article-title": "Biochemistry 13, 2307-2312. J.Am. chem",
      "volume": "84",
      "author": "Koch G. L. E.",
      "year": "1974",
      "journal-title": "Soc."
    },
    {
      "key": "p_18",
      "unstructured": "Leatherbarrow R. J. Fersht A. R. & Winter G. 1985 Proc. natn. Acad. Sci. U.S.A. (In the press.)"
    },
    {
      "key": "p_19",
      "doi-asserted-by": "crossref",
      "unstructured": "Lowe G. & Tansley G. 1984 Tetrahedron 40 113-117.",
      "DOI": "10.1016/0040-4020(84)85109-1"
    },
    {
      "key": "p_20",
      "first-page": "477",
      "article-title": "J. molec",
      "volume": "173",
      "author": "Monteilhet C.",
      "year": "1984",
      "journal-title": "Biol."
    },
    {
      "key": "p_21",
      "unstructured": "Pauling L. 1946 Chem. Engng"
    },
    {
      "key": "p_22",
      "first-page": "489",
      "article-title": "J. molec",
      "volume": "145",
      "author": "Rubin J.",
      "year": "1981",
      "journal-title": "Biol."
    },
    {
      "key": "p_23",
      "doi-asserted-by": "crossref",
      "unstructured": "Waye M. M. Y. Winter G. Wilkinson A. J. & Fersht A. R. 1983 EMBO J. 2 1827-1829.",
      "DOI": "10.1002/j.1460-2075.1983.tb01665.x"
    },
    {
      "key": "p_24",
      "doi-asserted-by": "crossref",
      "unstructured": "Wilkinson A. J. Fersht A. R. Blow D. M. & Winter G. 1983 Biochemistry 22 3581-3586.",
      "DOI": "10.1021/bi00284a007"
    },
    {
      "key": "p_25",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/307187a0"
    },
    {
      "key": "p_26",
      "first-page": "765",
      "article-title": "J.Am. chem",
      "volume": "106",
      "author": "Weiner S. J.",
      "year": "1984",
      "journal-title": "Soc."
    },
    {
      "key": "p_27",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/316656a0"
    },
    {
      "key": "p_28",
      "unstructured": "Wells T. N. C. & Fersht A. R. 1986 Biochemistry. (In the press.)"
    },
    {
      "key": "p_29",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/299756a0"
    },
    {
      "key": "p_30",
      "first-page": "383",
      "article-title": "Eur",
      "volume": "132",
      "author": "Winter G.",
      "year": "1983",
      "journal-title": "J. Biochem."
    }
  ],
  "container-title": "Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://royalsocietypublishing.org/doi/pdf/10.1098/rsta.1986.0041",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://royalsocietypublishing.org/doi/pdf/10.1098/rsta.1986.0041",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2021,
        2,
        21
      ]
    ],
    "date-time": "2021-02-21T01:13:04Z",
    "timestamp": 1613869984000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://royalsocietypublishing.org/doi/10.1098/rsta.1986.0041"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1986,
        4,
        30
      ]
    ]
  },
  "references-count": 30,
  "journal-issue": {
    "issue": "1540",
    "published-print": {
      "date-parts": [
        [
          1986,
          4,
          30
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1098/rsta.1986.0041"
  ],
  "URL": "http://dx.doi.org/10.1098/rsta.1986.0041",
  "relation": {},
  "ISSN": [
    "0080-4614",
    "2054-0272"
  ],
  "subject": [],
  "container-title-short": "Phil. Trans. R. Soc. Lond. A",
  "published": {
    "date-parts": [
      [
        1986,
        4,
        30
      ]
    ]
  }
}