The Structure of a Complex of Recombinant Hirudin and Human α-Thrombin
| Autor: | Alexander Tulinsky, Wolfram Bode, John W. Fenton, Carolyn Roitsch, Robert Huber, Timothy J. Rydel, K. G. Ravichandran |
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| Rok vydání: | 1990 |
| Předmět: |
Models
Molecular Hirudin Therapy Protein Conformation Stereochemistry Molecular Sequence Data Hirudin Crystal structure law.invention Thrombin X-Ray Diffraction law medicine Humans Amino Acid Sequence chemistry.chemical_classification Binding Sites Multidisciplinary biology Hydrogen bond Hirudins Recombinant Proteins Enzyme chemistry Enzyme inhibitor Recombinant DNA biology.protein Protein Binding medicine.drug |
| Zdroj: | Science. 249:277-280 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.2374926 |
| Popis: | The crystallographic structure of a recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (A) resolution. Hirudin consists of an NH2-terminal globular domain and a long (39 A) COOH-terminal extended domain. Residues Ile1 to Tyr3 of hirudin form a parallel beta-strand with Ser214 to Glu217 of thrombin with the nitrogen atom of Ile1 making a hydrogen bond with Ser195 O gamma atom of the catalytic site, but the specificity pocket of thrombin is not involved in the interaction. The COOH-terminal segment makes numerous electrostatic interactions with an anion-binding exosite of thrombin, whereas the last five residues are in a helical loop that forms many hydrophobic contacts. In all, 27 of the 65 residues of hirudin have contacts less than 4.0 A with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin. |
| Databáze: | OpenAIRE |
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