| Autor: | Laura R. Croal, Alexandrine M. Bilwes, Cindy M. Quezada, Melvin I. Simon, Brian R. Crane |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
chemistry.chemical_classification
biology Stereochemistry Histidine kinase Active site biology.organism_classification Biochemistry chemistry.chemical_compound chemistry Structural Biology Cyclic nucleotide-binding domain Thermotoga maritima Genetics biology.protein bacteria Nucleotide Binding site Adenosine triphosphate Histidine |
| Zdroj: | Nature Structural Biology. 8:353-360 |
| ISSN: | 1072-8368 |
| DOI: | 10.1038/86243 |
| Popis: | To probe the structural basis for protein histidine kinase (PHK) catalytic activity and the prospects for PHK-specific inhibitor design, we report the crystal structures for the nucleotide binding domain of Thermotoga maritima CheA with ADP and three ATP analogs (ADPNP, ADPCP and TNP-ATP) bound with either Mg2+ or Mn2+. The conformation of ADPNP bound to CheA and related ATPases differs from that reported in the ADPNP complex of PHK EnvZ. Interactions of the active site with the nucleotide bold gamma-phosphate and its associated Mg2+ ion are linked to conformational changes in an ATP-lid that could mediate recognition of the substrate domain. The inhibitor TNP-ATP binds CheA with its phosphates in a nonproductive conformation and its adenine and trinitrophenyl groups in two adjacent binding pockets. The trinitrophenyl interaction may be exploited for designing CheA-targeted drugs that would not interfere with host ATPases. |
| Databáze: | OpenAIRE |
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