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

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Citation

Tereshko V, Teplova M, Brunzelle J, Watterson DM, Egli M

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

Nat Struct Biol. 2001 Oct;8(10):899-907.

PubMed ID
11573098 [ View in PubMed
]
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 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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Death-associated protein kinase 1P53355Details