PDBsum entry 4gt4

Transferase

PDB id: 4gt4

Contents

Protein chain

274 a.a.

Ligands

NO3 ×4

Waters ×228

PDB id:

4gt4

Name:

Transferase

Title:

Structure of unliganded, inactive ror2 kinase domain

Structure:

Tyrosine-protein kinase transmembrane receptor ror2. Chain: a, b. Fragment: tyrosine kinase domain (unp residues 452-753). Synonym: neurotrophic tyrosine kinase, receptor-related 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ntrkr2, ror2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.41Å R-factor: 0.179 R-free: 0.205

Authors:

J.M.Mendrola,M.A.Lemmon

Key ref:

S.C.Artim et al. (2012). Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family. Biochem J, 448, 213-220. PubMed id: 22992069

Date:

28-Aug-12 Release date: 26-Sep-12

Protein chains

Q01974  (ROR2_HUMAN) -  Tyrosine-protein kinase transmembrane receptor ROR2 from Homo sapiens

Seq: 943 a.a.

Struc: 274 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

Biochem J 448:213-220 (2012)

PubMed id: 22992069

Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family.

S.C.Artim, J.M.Mendrola, M.A.Lemmon.

ABSTRACT

To investigate the range of autoinhibitory mechanisms used by TKDs (tyrosine kinase domains) from the insulin receptor family of RTKs (receptor tyrosine kinases), we determined crystal structures of TKDs from TrkA (tropomyosin receptor kinase A, a nerve growth factor receptor) and Ror2 (receptor tyrosine kinase-like orphan receptor 2, an unconventional Wnt receptor). TrkA autoinhibition closely resembles that seen for the insulin receptor, relying on projection of an activation loop tyrosine residue into the substrate-binding site and occlusion of the ATP-binding site by the activation loop. Ror2 employs similar mechanisms, but the unusual replacement of the phenylalanine residue in its Asp-Phe-Gly motif with leucine necessitates occlusion of the ATP-binding site by other means. The unusual Asp-Leu-Gly motif in Ror2 is displaced compared with other inactive kinases, allowing the activation loop to interact directly with the TKD's αC helix, in another mode of autoinhibition that is characteristic of the other extreme of this receptor family: ALK (anaplastic lymphoma kinase) and Met. These findings provide insight into the expected range of activating mutations in these TKDs in cancer. We also describe symmetrical dimers of the inactive TrkA TKD resembling those found in other RTKs, possibly reflecting an arrangement of kinase domains in a pre-formed TrkA dimer.