PDBsum entry 4yhj

Transferase

PDB id: 4yhj

Contents

Protein chains

501 a.a.

Ligands

AN2 ×2

Waters ×123

PDB id:

4yhj

Name:

Transferase

Title:

Structure and function of the hypertension variant a486v of g protein- coupled receptor kinase 4 (grk4)

Structure:

G protein-coupled receptor kinase 4. Chain: a, b. Synonym: g protein-coupled receptor kinase grk4,iti1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: grk4, gprk2l, gprk4. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.60Å R-factor: 0.200 R-free: 0.248

Authors:

S.J.Allen,G.Parthasarathy,S.Soisson,S.Munshi

Key ref:

S.J.Allen et al. (2015). Structure and Function of the Hypertension Variant A486V of G Protein-coupled Receptor Kinase 4. J Biol Chem, 290, 20360-20373. PubMed id: 26134571 DOI: 10.1074/jbc.M115.648907

Date:

27-Feb-15 Release date: 08-Jul-15

Protein chains

P32298  (GRK4_HUMAN) -  G protein-coupled receptor kinase 4 from Homo sapiens

Seq: 578 a.a.

Struc: 501 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.16 - [G-protein-coupled receptor] kinase.
• Reaction: [G-protein-coupled receptor] + ATP = [G-protein-coupled receptor]- phosphate + ADP + H⁺

[G-protein-coupled receptor] + ATP = [G-protein-coupled receptor]- phosphate + ADP (Bound ligand (Het Group name = AN2) matches with 92.86% similarity) + H(+)

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

Added reference

DOI no: 10.1074/jbc.M115.648907

J Biol Chem 290:20360-20373 (2015)

PubMed id: 26134571

Structure and Function of the Hypertension Variant A486V of G Protein-coupled Receptor Kinase 4.

S.J.Allen, G.Parthasarathy, P.L.Darke, R.E.Diehl, R.E.Ford, D.L.Hall, S.A.Johnson, J.C.Reid, K.W.Rickert, J.M.Shipman, S.M.Soisson, P.Zuck, S.K.Munshi, K.J.Lumb.

ABSTRACT

G-protein-coupled receptor (GPCR) kinases (GRKs) bind to and phosphorylate GPCRs, initiating the process of GPCR desensitization and internalization. GRK4 is implicated in the regulation of blood pressure, and three GRK4 polymorphisms (R65L, A142V, and A486V) are associated with hypertension. Here, we describe the 2.6 Å structure of human GRK4α A486V crystallized in the presence of 5'-adenylyl β,γ-imidodiphosphate. The structure of GRK4α is similar to other GRKs, although slight differences exist within the RGS homology (RH) bundle subdomain, substrate-binding site, and kinase C-tail. The RH bundle subdomain and kinase C-terminal lobe form a strikingly acidic surface, whereas the kinase N-terminal lobe and RH terminal subdomain surfaces are much more basic. In this respect, GRK4α is more similar to GRK2 than GRK6. A fully ordered kinase C-tail reveals interactions linking the C-tail with important determinants of kinase activity, including the αB helix, αD helix, and the P-loop. Autophosphorylation of wild-type GRK4α is required for full kinase activity, as indicated by a lag in phosphorylation of a peptide from the dopamine D1 receptor without ATP preincubation. In contrast, this lag is not observed in GRK4α A486V. Phosphopeptide mapping by mass spectrometry indicates an increased rate of autophosphorylation of a number of residues in GRK4α A486V relative to wild-type GRK4α, including Ser-485 in the kinase C-tail.