PDBsum entry 4tnb

Signaling protein

PDB id: 4tnb

Contents

Protein chain

529 a.a.

Ligands

SGV

Waters ×398

PDB id:

4tnb

Name:

Signaling protein

Title:

Crystal structure of g protein-coupled receptor kinase 5 in complex with sangivamycin

Structure:

G protein-coupled receptor kinase 5. Chain: a. Synonym: g protein-coupled receptor kinase grk5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: grk5, gprk5. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.11Å R-factor: 0.175 R-free: 0.232

Authors:

A.Bhardwaj,K.E.Komolov,J.L.Benovic

Key ref:

K.E.Komolov et al. (2015). Atomic Structure of GRK5 Reveals Distinct Structural Features Novel for G Protein-coupled Receptor Kinases. J Biol Chem, 290, 20629-20647. PubMed id: 26032409 DOI: 10.1074/jbc.M115.647297

Date:

03-Jun-14 Release date: 10-Jun-15

Protein chain

P34947  (GRK5_HUMAN) -  G protein-coupled receptor kinase 5 from Homo sapiens

Seq: 590 a.a.

Struc: 529 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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 = SGV) matches with 58.06% similarity) + H(+)

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

Added reference

DOI no: 10.1074/jbc.M115.647297

J Biol Chem 290:20629-20647 (2015)

PubMed id: 26032409

Atomic Structure of GRK5 Reveals Distinct Structural Features Novel for G Protein-coupled Receptor Kinases.

K.E.Komolov, A.Bhardwaj, J.L.Benovic.

ABSTRACT

G protein-coupled receptor kinases (GRKs) are members of the protein kinase A, G, and C families (AGC) and play a central role in mediating G protein-coupled receptor phosphorylation and desensitization. One member of the family, GRK5, has been implicated in several human pathologies, including heart failure, hypertension, cancer, diabetes, and Alzheimer disease. To gain mechanistic insight into GRK5 function, we determined a crystal structure of full-length human GRK5 at 1.8 Å resolution. GRK5 in complex with the ATP analog 5'-adenylyl β,γ-imidodiphosphate or the nucleoside sangivamycin crystallized as a monomer. The C-terminal tail (C-tail) of AGC kinase domains is a highly conserved feature that is divided into three segments as follows: the C-lobe tether, the active-site tether (AST), and the N-lobe tether (NLT). This domain is fully resolved in GRK5 and reveals novel interactions with the nucleotide and N-lobe. Similar to other AGC kinases, the GRK5 AST is an integral part of the nucleotide-binding pocket, a feature not observed in other GRKs. The AST also mediates contact between the kinase N- and C-lobes facilitating closure of the kinase domain. The GRK5 NLT is largely displaced from its previously observed position in other GRKs. Moreover, although the autophosphorylation sites in the NLT are >20 Å away from the catalytic cleft, they are capable of rapid cis-autophosphorylation suggesting high mobility of this region. In summary, we provide a snapshot of GRK5 in a partially closed state, where structural elements of the kinase domain C-tail are aligned to form novel interactions to the nucleotide and N-lobe not previously observed in other GRKs.