Structural insight into nucleotide recognition by human death-associated protein kinase

Journal Article · Mon Jun 01 04:00:00 EDT 2009 · Acta Crystallogr. D

DOI:https://doi.org/10.1107/S0907444908043679· OSTI ID:1005592

McNamara, Laurie K; Watterson, D M; Brunzelle, Joseph S

Death-associated protein kinase (DAPK) is a member of the Ca{sup 2+}/calmodulin-regulated family of serine/threonine protein kinases. The role of the kinase activity of DAPK in eukaryotic cell apoptosis and the ability of bioavailable DAPK inhibitors to rescue neuronal death after brain injury have made it a drug-discovery target for neurodegenerative disorders. In order to understand the recognition of nucleotides by DAPK and to gain insight into DAPK catalysis, the crystal structure of human DAPK was solved in complex with ADP and Mg{sup 2+} at 1.85 {angstrom} resolution. ADP is a product of the kinase reaction and product release is considered to be the rate-limiting step of protein kinase catalytic cycles. The structure of DAPK-ADP-Mg{sup 2+} was compared with a newly determined DAPK-AMP-PNP-Mg{sup 2+} structure and the previously determined apo DAPK structure (PDB code 1 jks). The comparison shows that nucleotide-induced changes are localized to the glycine-rich loop region of DAPK.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005592
• Journal Information: Acta Crystallogr. D, Journal Name: Acta Crystallogr. D Journal Issue: (3) ; 03, 2009 Vol. 65; ISSN 0907-4449
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ADP
APOPTOSIS
BRAIN
CATALYSIS
CRYSTAL STRUCTURE
DEATH
GAIN
HUMAN POPULATIONS
NUCLEOTIDES
PHOSPHOTRANSFERASES
PROTEINS
RESOLUTION