Crystal Structures of the Catalytic Domain of Human Protein Kinase Associated with Apoptosis and Tumor Suppression
- Northwestern
We have determined X-ray crystal structures with up to 1.5 {angstrom} resolution of the catalytic domain of death-associated protein kinase (DAPK), the first described member of a novel family of pro-apoptotic and tumor-suppressive serine/threonine kinases. The geometry of the active site was studied in the apo form, in a complex with nonhydrolyzable AMPPnP and in a ternary complex consisting of kinase, AMPPnP and either Mg{sup 2+} or Mn{sup 2+}. The structures revealed a previously undescribed water-mediated stabilization of the interaction between the lysine that is conserved in protein kinases and the {beta}- and {gamma}-phosphates of ATP, as well as conformational changes at the active site upon ion binding. Comparison between these structures and nucleotide triphosphate complexes of several other kinases disclosed a number of unique features of the DAPK catalytic domain, among which is a highly ordered basic loop in the N-terminal domain that may participate in enzyme regulation.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1006370
- Journal Information:
- Nat. Struct. Mol. Biol., Journal Name: Nat. Struct. Mol. Biol. Journal Issue: 2001 Vol. 8
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Structural insight into nucleotide recognition by human death-associated protein kinase
[Characterization of a putative S locus encoded receptor protein kinase and its role in self-incompatibility]