| Autor: | David Reverter, Tad A. Holak, Carlos Fernandez-Catalan, Roland Baumgartner, Francesc X. Avilés, Ruth Pfänder, Josep Vendrell, Wolfram Bode, Robert Huber |
|---|---|
| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Nature Structural Biology. 7:322-328 |
| ISSN: | 1072-8368 |
| DOI: | 10.1038/74092 |
| Popis: | Leech carboxypeptidase inhibitor (LCI) is a novel protein inhibitor present in the medicinal leech Hirudo medicinalis. The structures of LCI free and bound to carboxypeptidase A2 (CPA2)have been determined by NMR and X-ray crystallography, respectively. The LCI structure defines a new protein motif that comprises a five-stranded antiparallel β-sheet and one short α-helix. This structure is preserved in the complex with human CPA2 in the X-ray structure, where the contact regions between the inhibitor and the protease are defined. The C-terminal tail of LCI becomes rigid upon binding the protease as shown in the NMR relaxation studies, and it interacts with the carboxypeptidase in a substrate-like manner. The homology between the C-terminal tails of LCI and the potato carboxypeptidase inhibitor represents a striking example of convergent evolution dictated by the target protease. These new structures are of biotechnological interest since they could elucidate the control mechanism of metallo-carboxypeptidases and could be used as lead compounds for the search of fibrinolytic drugs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|