PDBsum entry 3f5g

Transferase

PDB id: 3f5g

Contents

Protein chain

280 a.a. *

Ligands

ADP

Metals

_MG

Waters ×133

* Residue conservation analysis

PDB id:

3f5g

Name:

Transferase

Title:

Crystal structure of death associated protein kinase in complex with adp and mg2+

Structure:

Death-associated protein kinase 1. Chain: a. Fragment: unp residues 2-285, protein kinase domain,catalytic domain. Synonym: dap kinase 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dapk, dapk1, death-associated protein kinase 1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.85Å R-factor: 0.188 R-free: 0.244

Authors:

L.K.Mcnamara,D.M.Watterson,J.S.Brunzelle

Key ref:

L.K.McNamara et al. (2009). Structural insight into nucleotide recognition by human death-associated protein kinase. Acta Crystallogr D Biol Crystallogr, 65, 241-248. PubMed id: 19237746 DOI: 10.1107/S0907444908043679

Date:

03-Nov-08 Release date: 24-Mar-09

Protein chain

P53355  (DAPK1_HUMAN) -  Death-associated protein kinase 1 from Homo sapiens

Seq: 1430 a.a.

Struc: 280 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1107/S0907444908043679

Acta Crystallogr D Biol Crystallogr 65:241-248 (2009)

PubMed id: 19237746

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

L.K.McNamara, D.M.Watterson, J.S.Brunzelle.

ABSTRACT

Death-associated protein kinase (DAPK) is a member of the Ca(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(2+) at 1.85 A 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(2+) was compared with a newly determined DAPK-AMP-PNP-Mg(2+) structure and the previously determined apo DAPK structure (PDB code 1jks). The comparison shows that nucleotide-induced changes are localized to the glycine-rich loop region of DAPK.

Selected figure(s)

Figure 2.
Figure 2 Superposition by least-squares fitting of DAPK-ADP-Mg^2+ and apo DAPK reveals little change between the two structures apart from in two key areas: the hinge region near Ala97 and the glycine-rich loop near Ser21. The DAPK-ADP-Mg^2+ structure is shown in red and the apo DAPK structure is shown in beige. Protein residues from the N-terminal domain and hinge region are shown.

Figure 5.
Figure 5 Comparisons of the glycine-rich loop. (a) Superposition of the glycine-rich loops of apo DAPK (beige), DAPK-ADP-Mg^2+ (red) and DAPK-AMP-PNP-Mg^2+ (blue) and their position relative to the nucleotide. The DAPK-AMP-PNP-Mg^2+ loop has the most closed conformation. Residues 17-28 are shown for simplicity. The calculated r.m.s. deviation over the C^ atoms of residues 20-25 between the apo DAPK structure and the DAPK-AMP-PNP-Mg^2+ structure is 1.03 Å and that between the apo DAPK and DAPK-ADP-Mg^2+ structures is 0.62 Å. (b) 2F[o] - F[c] electron-density map at 1.0 of the glycine-rich loop of DAPK-ADP-Mg^2+. One conformation of Gln23 is modeled such that the side chain is within proximity of the -phosphate (conformation B). (c) 2F[o] - F[c] electron-density map of the glycine-rich loop of DAPK-AMP-PNP-Mg^2+. The side chain of Phe24 in the DAPK-AMP-PNP structure can be modeled in the `open' conformation (B) or a conformationally restricted position (A).

The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallogr D Biol Crystallogr (2009, 65, 241-248) copyright 2009.

Figures were selected by an automated process.