PDBsum entry 3nyn

Transferase

PDB id

3nyn

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Contents

			Protein chain

					554 a.a. *

			Ligands

					SGV ×2


					SO4 ×14


					BU3 ×2

			Waters ×12

* Residue conservation analysis

PDB id:

3nyn

Links

Name:

Transferase

Title:

Crystal structure of g protein-coupled receptor kinase 6 in complex with sangivamycin

Structure:

G protein-coupled receptor kinase 6. Chain: a, b. Synonym: g protein-coupled receptor kinase grk6. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gprk6, grk6. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

2.72Å

R-factor:

0.227

R-free:

0.238

Authors:

J.J.G.Tesmer,P.Singh

Key ref:

C.A.Boguth et al. (2010). Molecular basis for activation of G protein-coupled receptor kinases. Embo J, 29, 3249-3259. PubMed id: 20729810

Date:

15-Jul-10

Release date:

22-Sep-10

PROCHECK

	Headers

	References

Protein chains

P43250 (GRK6_HUMAN) - G protein-coupled receptor kinase 6 from Homo sapiens

Seq: Struc:

Seq: Struc:					576 a.a. 553 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.7.11.16 - [G-protein-coupled receptor] kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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

	Embo J 29:3249-3259 (2010)
PubMed id: 20729810

Molecular basis for activation of G protein-coupled receptor kinases.
C.A.Boguth, P.Singh, C.C.Huang, J.J.Tesmer.

ABSTRACT

G protein-coupled receptor (GPCR) kinases (GRKs) selectively recognize and are allosterically regulated by activated GPCRs, but the molecular basis for this interaction is not understood. Herein, we report crystal structures of GRK6 in which regions known to be critical for receptor phosphorylation have coalesced to stabilize the kinase domain in a closed state and to form a likely receptor docking site. The crux of this docking site is an extended N-terminal helix that bridges the large and small lobes of the kinase domain and lies adjacent to a basic surface of the protein proposed to bind anionic phospholipids. Mutation of exposed, hydrophobic residues in the N-terminal helix selectively inhibits receptor, but not peptide phosphorylation, suggesting that these residues interact directly with GPCRs. Our structural and biochemical results thus provide an explanation for how receptor recognition, phospholipid binding, and kinase activation are intimately coupled in GRKs.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21265573

C.C.Huang, T.Orban, B.Jastrzebska, K.Palczewski, and J.J.Tesmer (2011).
Activation of G protein-coupled receptor kinase 1 involves interactions between its N-terminal region and its kinase domain.

Biochemistry, 50, 1940-1949.

PDB code:

3qc9

21256157

R.Eglen, and T.Reisine (2011).
Drug discovery and the human kinome: recent trends.

Pharmacol Ther, 130, 144-156.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.