PDBsum entry 1bak

Transferase

PDB id: 1bak

Contents

Protein chain

119 a.a. *

* Residue conservation analysis

PDB id:

1bak

Name:

Transferase

Title:

Signal transduction pleckstrin homology domain of g-protein coupled receptor kinase 2 (beta-adrenergic receptor kinase 1), c-terminal extended, nmr, 20 structures

Structure:

G-protein coupled receptor kinase 2. Chain: a. Fragment: c-terminal extended pleckstrin homology domain. Synonym: grk-2, beta-adrenergic receptor kinase 1, beta-ark 1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

20 models

Authors:

D.Fushman,D.Cowburn

Key ref:

D.Fushman et al. (1998). The solution structure and dynamics of the pleckstrin homology domain of G protein-coupled receptor kinase 2 (beta-adrenergic receptor kinase 1). A binding partner of Gbetagamma subunits. J Biol Chem, 273, 2835-2843. PubMed id: 9446593 DOI: 10.1074/jbc.273.5.2835

Date:

21-Nov-97 Release date: 25-Feb-98

Protein chain

P25098  (ARBK1_HUMAN) -  Beta-adrenergic receptor kinase 1 from Homo sapiens

Seq: 689 a.a.

Struc: 119 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.2.7.11.15 - [beta-adrenergic-receptor] kinase.
• Reaction: [beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-phosphate + ADP + H⁺

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

reference

DOI no: 10.1074/jbc.273.5.2835

J Biol Chem 273:2835-2843 (1998)

PubMed id: 9446593

The solution structure and dynamics of the pleckstrin homology domain of G protein-coupled receptor kinase 2 (beta-adrenergic receptor kinase 1). A binding partner of Gbetagamma subunits.

D.Fushman, T.Najmabadi-Haske, S.Cahill, J.Zheng, H.LeVine, D.Cowburn.

ABSTRACT

The solution structure of an extended pleckstrin homology (PH) domain from the beta-adrenergic receptor kinase is obtained by high resolution NMR. The structure establishes that the beta-adrenergic receptor kinase extended PH domain has the same fold and topology as other PH domains, and there are several unique features, most notably an extended C-terminal alpha-helix that behaves as a molten helix, and a surface charge polarity that is extensively modified by positive residues in the extended alpha-helix and the C terminus. These observations complement biochemical evidence that the C-terminal portion of this PH domain participates in protein-protein interactions with Gbetagamma subunits. This suggests that the C-terminal segment of the PH domain may function to mediate protein-protein interactions with the targets of PH domains.

Selected figure(s)

Figure 1.
Fig. 1. The sequence of the protein construct used in the present work and its relation to the nominal PH domain and to the G[ ]-binding region of ARK1. At the top is the nominal length PH domain section; below is the domain demonstrated previously (50) to be sufficient and optimal for G[ ]binding, below which is the construct used here, which has the same G[ ]binding. The lowercase "gshm" residues are from the GST construct, and^ are not further referred to. At the bottom, the complete sequence^ of h ARK1 PH domain, and the similar h ARK2 are compared, with the secondary structural elements of h ARK1 superimposed in color. The more flexible region of the C-terminal -helix is shown in light blue.

Figure 4.
Fig. 4. The effect of the C terminus on the electrostatic potential of the h ARK1 PH domain, and comparison with the PLC PH domain. Surfaces are contoured at 2 kT/e (red) and 2 kT/e (blue) (GRASP; Ref. 56) for various lengths of the C-terminal extension: a, full-length construct, 556-670; b, residues 556-666; c, residues 556-661; d, residues 556-656; e, nominal PH domain, residues 556-651. The ARK1 PH domain constructs in b-d correspond to C-terminal deletion studies of G[ ]binding (b and c (50) and d^ (19)). The most C-terminal residues, upon truncation, are indicated. For comparison, the electrostatic potential of the PH domain from PLC (Protein Data Bank entry 1MAI) is shown in f; the arrow indicates a positively charged area at the opening of the -barrel, which is involved in the phospholipid binding (8). The molecular orientations are similar, as indicated by the backbone tube diagrams.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1998, 273, 2835-2843) copyright 1998.

Figures were selected by an automated process.