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Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin.

1995; Springer Nature; Volume: 14; Issue: 21 Linguagem: Inglês

10.1002/j.1460-2075.1995.tb00199.x

1460-2075

Andreas van de Locht, Doriano Lamba, Margit Bauer, Robert Huber, Thomas Friedrich, Burkhard Kröger, W. Höffken, Wolfram Bode,

Neurobiology and Insect Physiology Research

Research Article1 November 1995free access Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin. A. van de Locht A. van de Locht Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author D. Lamba D. Lamba Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author M. Bauer M. Bauer Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author R. Huber R. Huber Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author T. Friedrich T. Friedrich Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author B. Kröger B. Kröger Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author W. Höffken W. Höffken Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author W. Bode W. Bode Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author A. van de Locht A. van de Locht Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author D. Lamba D. Lamba Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author M. Bauer M. Bauer Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author R. Huber R. Huber Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author T. Friedrich T. Friedrich Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author B. Kröger B. Kröger Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author W. Höffken W. Höffken Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author W. Bode W. Bode Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. Search for more papers by this author Author Information A. Locht1, D. Lamba1, M. Bauer1, R. Huber1, T. Friedrich1, B. Kröger1, W. Höffken1 and W. Bode1 1Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany. The EMBO Journal (1995)14:5149-5157https://doi.org/10.1002/j.1460-2075.1995.tb00199.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin bug Rhodnius prolixus. The 2.6 Angstrum crystal structure of the non-covalent complex between recombinant rhodniin and bovine alpha-thrombin reveals that the two Kazal-type domains of rhodniin bind to different sites of thrombin. The amino-terminal domain binds in a substrate-like manner to the narrow active-site cleft of thrombin; the imidazole group of the P1 His residue extends into the S1 pocket to form favourable hydrogen/ionic bonds with Asp189 at its bottom, and additionally with Glu192 at its entrance. The carboxy-terminal domain, whose distorted reactive-site loop cannot adopt the canonical conformation, docks to the fibrinogen recognition exosite via extensive electrostatic interactions. The rather acidic polypeptide linking the two domains is displaced from the thrombin surface, with none of its residues involved in direct salt bridges with thrombin. The tight (Ki = 2 × 10(-13) M) binding of rhodniin to thrombin is the result of the sum of steric and charge complementarity of the amino-terminal domain towards the active-site cleft, and of the electrostatic interactions between the carboxy-terminal domain and the exosite. Previous ArticleNext Article Volume 14Issue 211 November 1995In this issue RelatedDetailsLoading ...