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The Structure of a Complex of Recombinant Hirudin and Human α-Thrombin
Abstract
The crystallographic structure of a recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (Å) resolution. Hirudin consists of an NH 2 -terminal globular domain and a long (39 Å) COOH-terminal extended domain. Residues Ile 1 to Tyr 3 of hirudin form a parallel β-strand with Ser 214 to Glu 217 of thrombin with the nitrogen atom of Ile 1 making a hydrogen bond with Ser 195 Oγ 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 Å with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin.
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Cited by
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Eckelman, B. P., Salvesen, G. S., & Scott, F. L. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400795 · Cited by 813
A player of many parts: The spotlight falls on thrombin's structure
Stubbs, M. T., & Bode, W. (1993) · Thrombosis Research · doi:10.1016/0049-3848(93)90002-6 · Cited by 441
Self-citationBanner, D. W., & Hadváry, P. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54894-8 · Cited by 325
Metadata
- Authors
- Rydel, T. J., Ravichandran, K. G., Tulinsky, A., Bode, W., Huber, R., Roitsch, C., & Fenton, J. W.
- Venue
- Science
- Published
- 1990-07-20
- Volume
- 249
- Issue
- 4966
- Pages
- 277-280
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2141373630
- Cited by
- 709
- References
- 0
- FWCI
- 43.77
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: The Structure of a Complex of Recombinant Hirudin and Human α-Thrombin. https://app.cochat.ai/papers/10.1126/science.2374926
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- Rydel, T. J., Ravichandran, K. G., Tulinsky, A., Bode, W., Huber, R., Roitsch, C., & Fenton, J. W. (1990). The Structure of a Complex of Recombinant Hirudin and Human α-Thrombin. Science. https://doi.org/10.1126/science.2374926
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
