Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression

Valentina Tereshko, Marianna Teplova, Joseph Brunzelle, D. Martin Watterson, Martin Egli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

We have determined X-ray crystal structures with up to 1.5 A 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 Mg2+ or Mn2+. The structures revealed a previously undescribed water-mediated stabilization of the interaction between the lysine that is conserved in protein kinases and the βand γ-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.

Original languageEnglish (US)
Pages (from-to)899-907
Number of pages9
JournalNature Structural Biology
Volume8
Issue number10
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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