DOI: 10.1016/0014-5793(84)81085-6. The active site of aspartic proteinases

10.1016/0014-5793(84)81085-6

Crossref journal-article

Wiley

FEBS Letters (311)

Abstract

The active site of the aspartic proteinase, endothiapepsin, has been defined by X‐ray analysis and restrained least‐squares refinement at 2.1 Å resolution with a crystallographic agreement value of 0.16. The environments of the two catalytically important aspartyl groups are remarkably similar and the contributions of the NH2‐ and COOH‐terminal domains to the catalytic centre are related by a local 2‐fold axis. The carboxylates of the aspartyls share a hydrogen bond and have equivalent contacts to a bound water molecule or hydroxonium ion lying on the local diad. The main chains around 32 and 215 are connected by a novel interaction involving diad‐related threonines. It is suggested that the two pK a, values of the active site aspartyls arise from a structure not unlike that in maleic acid with a hydrogen‐bonded intermediate species and a dicarboxylate characterised by electrostatic repulsions between the two negatively charged groups.

Bibliography

Pearl, L., & Blundell, T. (1984). The active site of aspartic proteinases. FEBS Letters, 174(1), 96â101. Portico.

Authors 2

Laurence Pearl (first)
Tom Blundell (additional)

References 28 Referenced 210

10.1007/978-1-4757-0719-9
10.1073/pnas.74.2.556
10.1038/266140a0
10.1007/978-1-4757-0719-9_2
{'key': 'e_1_2_1_6_1', 'first-page': '81', 'volume': '52', 'author': 'Blundell T.L.', 'year': '1979', 'journal-title': 'Fed. Eur. Biochem. Soc.'} / Fed. Eur. Biochem. Soc. by Blundell T.L. (1979)
10.1007/978-1-4757-0719-9_4
10.1139/o80-035
{'key': 'e_1_2_1_9_1', 'first-page': '350', 'volume-title': 'Structural Studies on Molecules of Biological Interest', 'author': 'James M.N.G.', 'year': '1981'} / Structural Studies on Molecules of Biological Interest by James M.N.G. (1981)
10.1073/pnas.70.12.3437
10.1038/267808a0
10.1016/B978-0-08-024417-4.50030-5
10.1016/0022-2836(83)90008-6
10.1016/S0022-2836(75)80173-2
Pearl L.H. Jenkins J.A. Sewell B.T. Pedersen V. and Blundell T.L. (1984) in preparation.
10.1063/1.1750302
Hollaway M. (1984) personal communication.
10.1038/271618a0
{'key': 'e_1_2_1_19_1', 'first-page': '119', 'volume-title': 'The Enzymes', 'author': 'Fruton J.S.', 'year': '1981'} / The Enzymes by Fruton J.S. (1981)
10.1073/pnas.79.16.4858
10.1038/298090a0
10.1073/pnas.80.24.7405
10.1093/nar/11.20.7181
{'key': 'e_1_2_1_24_1', 'author': 'Hobart P.M.', 'year': '1980', 'journal-title': 'Proc. Natl. Acad. Sci. USA'} / Proc. Natl. Acad. Sci. USA by Hobart P.M. (1980)
10.1021/bi00269a052
10.1002/9780470122891.ch1
10.1073/pnas.79.20.6137
10.1101/SQB.1972.036.01.013
10.1016/0022-2836(83)90030-X

Dates

Type	When
Created	23 years ago (July 25, 2002, 5:12 a.m.)
Deposited	1 year, 11 months ago (Sept. 16, 2023, 3:41 a.m.)
Indexed	2 weeks, 5 days ago (Aug. 2, 2025, 12:25 a.m.)
Issued	41 years ago (Aug. 20, 1984)
Published	41 years ago (Aug. 20, 1984)
Published Online	23 years, 9 months ago (Nov. 2, 2001)
Published Print	41 years ago (Aug. 20, 1984)

Funders 0

None

BibTeX

@article{Pearl_1984, title={The active site of aspartic proteinases}, volume={174}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/0014-5793(84)81085-6}, DOI={10.1016/0014-5793(84)81085-6}, number={1}, journal={FEBS Letters}, publisher={Wiley}, author={Pearl, Laurence and Blundell, Tom}, year={1984}, month=aug, pages={96–101} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        2
      ]
    ],
    "date-time": "2025-08-02T04:25:51Z",
    "timestamp": 1754108751648
  },
  "reference-count": 28,
  "publisher": "Wiley",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2001,
            11,
            2
          ]
        ],
        "date-time": "2001-11-02T00:00:00Z",
        "timestamp": 1004659200000
      },
      "content-version": "vor",
      "delay-in-days": 6283,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1984,
        8,
        20
      ]
    ]
  },
  "abstract": "<jats:p>The active site of the aspartic proteinase, endothiapepsin, has been defined by X\u2010ray analysis and restrained least\u2010squares refinement at 2.1 \u00c5 resolution with a crystallographic agreement value of 0.16. The environments of the two catalytically important aspartyl groups are remarkably similar and the contributions of the NH<jats:sub>2</jats:sub>\u2010 and COOH\u2010terminal domains to the catalytic centre are related by a local 2\u2010fold axis. The carboxylates of the aspartyls share a hydrogen bond and have equivalent contacts to a bound water molecule or hydroxonium ion lying on the local diad. The main chains around 32 and 215 are connected by a novel interaction involving diad\u2010related threonines. It is suggested that the two p<jats:italic>K</jats:italic>\n<jats:sub>a</jats:sub>, values of the active site aspartyls arise from a structure not unlike that in maleic acid with a hydrogen\u2010bonded intermediate species and a dicarboxylate characterised by electrostatic repulsions between the two negatively charged groups.</jats:p>",
  "DOI": "10.1016/0014-5793(84)81085-6",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        25
      ]
    ],
    "date-time": "2002-07-25T09:12:22Z",
    "timestamp": 1027588342000
  },
  "page": "96-101",
  "source": "Crossref",
  "is-referenced-by-count": 210,
  "title": "The active site of aspartic proteinases",
  "prefix": "10.1002",
  "volume": "174",
  "author": [
    {
      "given": "Laurence",
      "family": "Pearl",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Tom",
      "family": "Blundell",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2001,
        11,
        2
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_1_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/978-1-4757-0719-9"
    },
    {
      "key": "e_1_2_1_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.74.2.556"
    },
    {
      "key": "e_1_2_1_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/266140a0"
    },
    {
      "key": "e_1_2_1_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/978-1-4757-0719-9_2"
    },
    {
      "key": "e_1_2_1_6_1",
      "first-page": "81",
      "volume": "52",
      "author": "Blundell T.L.",
      "year": "1979",
      "journal-title": "Fed. Eur. Biochem. Soc."
    },
    {
      "key": "e_1_2_1_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/978-1-4757-0719-9_4"
    },
    {
      "key": "e_1_2_1_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1139/o80-035"
    },
    {
      "key": "e_1_2_1_9_1",
      "first-page": "350",
      "volume-title": "Structural Studies on Molecules of Biological Interest",
      "author": "James M.N.G.",
      "year": "1981"
    },
    {
      "key": "e_1_2_1_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.70.12.3437"
    },
    {
      "key": "e_1_2_1_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/267808a0"
    },
    {
      "key": "e_1_2_1_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/B978-0-08-024417-4.50030-5"
    },
    {
      "key": "e_1_2_1_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(83)90008-6"
    },
    {
      "key": "e_1_2_1_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(75)80173-2"
    },
    {
      "key": "e_1_2_1_15_1",
      "unstructured": "Pearl L.H. Jenkins J.A. Sewell B.T. Pedersen V. and Blundell T.L. (1984) in preparation."
    },
    {
      "key": "e_1_2_1_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.1750302"
    },
    {
      "key": "e_1_2_1_17_1",
      "unstructured": "Hollaway M. (1984) personal communication."
    },
    {
      "key": "e_1_2_1_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/271618a0"
    },
    {
      "key": "e_1_2_1_19_1",
      "first-page": "119",
      "volume-title": "The Enzymes",
      "author": "Fruton J.S.",
      "year": "1981"
    },
    {
      "key": "e_1_2_1_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.79.16.4858"
    },
    {
      "key": "e_1_2_1_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/298090a0"
    },
    {
      "key": "e_1_2_1_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.80.24.7405"
    },
    {
      "key": "e_1_2_1_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/11.20.7181"
    },
    {
      "key": "e_1_2_1_24_1",
      "author": "Hobart P.M.",
      "year": "1980",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "e_1_2_1_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00269a052"
    },
    {
      "key": "e_1_2_1_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/9780470122891.ch1"
    },
    {
      "key": "e_1_2_1_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.79.20.6137"
    },
    {
      "key": "e_1_2_1_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/SQB.1972.036.01.013"
    },
    {
      "key": "e_1_2_1_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(83)90030-X"
    }
  ],
  "container-title": "FEBS Letters",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2F0014-5793%2884%2981085-6",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2F0014-5793(84)81085-6",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2884%2981085-6",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        9,
        16
      ]
    ],
    "date-time": "2023-09-16T07:41:51Z",
    "timestamp": 1694850111000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://febs.onlinelibrary.wiley.com/doi/10.1016/0014-5793%2884%2981085-6"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1984,
        8,
        20
      ]
    ]
  },
  "references-count": 28,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          1984,
          8,
          20
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1016/0014-5793(84)81085-6"
  ],
  "URL": "http://dx.doi.org/10.1016/0014-5793(84)81085-6",
  "relation": {},
  "ISSN": [
    "0014-5793",
    "1873-3468"
  ],
  "subject": [],
  "container-title-short": "FEBS Letters",
  "published": {
    "date-parts": [
      [
        1984,
        8,
        20
      ]
    ]
  }
}