Interactions of a new α-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition
| Autor: | Huixiong Chen, Marie-Claude Fournie-Zaluski, Mohamed Selkti, Bernard-Pierre Roques, Alain Tomas, Thierry Prangé, Jean-François Gaucher |
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| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Protein Conformation Stereochemistry Thermolysin chemistry.chemical_element Zinc Crystallography X-Ray 010402 general chemistry 01 natural sciences Structure-Activity Relationship chemistry.chemical_compound Organophosphorus Compounds Structural Biology Moiety Enzyme Inhibitors chemistry.chemical_classification Binding Sites biology 010405 organic chemistry Metalloendopeptidases Active site General Medicine Exopeptidase 0104 chemical sciences Enzyme chemistry biology.protein Metalloendopeptidase Crystallization Derivative (chemistry) Protein Binding |
| Zdroj: | Acta Crystallographica Section D Biological Crystallography. 59:1200-1205 |
| ISSN: | 0907-4449 |
| Popis: | A new alpha-aminophosphinic compound able to inhibit both zinc-containing exopeptidases and endopeptidases has been crystallized with TLN as a model in order to investigate the mode of zinc recognition by the phosphinic moiety and to evaluate the potential role of the free alpha-amino group in the formation of enzyme-inhibitor complexes. In addition to the main interactions between the backbone of the inhibitor and the enzyme active site, it is observed that the phosphinic group acts as a distorted bidentate ligand for the zinc ion, while the free alpha-amino function does not directly participate in interactions within the active site. Association of the present data and the K(i) values of various analogues of the inhibitor towards TLN and neprilysin suggests differences in the hydrophobicity of the S(1)-S(2) domains of the enzymes. This could be taken into account in the design of selective inhibitors. |
| Databáze: | OpenAIRE |
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