PDBsum entry 2z8c

Transferase

PDB id: 2z8c

Contents

Protein chain

300 a.a. *

Ligands

ASP-TYR-MET-ASN-MET-SER

S91

* Residue conservation analysis

PDB id:

2z8c

Name:

Transferase

Title:

Phosphorylated insulin receptor tyrosine kinase in complex with (4- {[5-carbamoyl-4-(3-methylanilino)pyrimidin-2-yl]amino}phenyl)acetic acid

Structure:

Insulin receptor. Chain: a. Fragment: tyrosine kinase domain. Synonym: ir, cd220 antigen. Engineered: yes. Mutation: yes. 6-mer peptide from insulin receptor substrate 1. Chain: b. Synonym: irs-1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: insr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: irs1.

Resolution:

3.25Å R-factor: 0.217 R-free: 0.292

Authors:

N.Katayama,H.Kurihara

Key ref:

N.Katayama et al. (2008). Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors. Proteins, 73, 795-801. PubMed id: 18767165 DOI: 10.1002/prot.22207

Date:

05-Sep-07 Release date: 12-Aug-08

Protein chain

P06213  (INSR_HUMAN) -  Insulin receptor from Homo sapiens

Seq: 1382 a.a.

Struc: 300 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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

DOI no: 10.1002/prot.22207

Proteins 73:795-801 (2008)

PubMed id: 18767165

Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors.

N.Katayama, M.Orita, T.Yamaguchi, H.Hisamichi, S.Kuromitsu, H.Kurihara, H.Sakashita, Y.Matsumoto, S.Fujita, T.Niimi.

ABSTRACT

In this article, we report crystal structures for inhibitor-kinase complexes in which the inhibitor has different binding orientations and hydrogen-bonding patterns with extracellular-signal regulated kinase 2 and insulin receptor tyrosine kinase. Our crystallographic studies, and sequence and structural analyses of 532 coordinates of kinases held in the Protein Data Bank, suggest that the length of the "specificity linker" described here is a key structural element of the hydrogen-bonding patterns between protein kinases and their inhibitors. Proteins 2008. (c) 2008 Wiley-Liss, Inc.

Selected figure(s)

Figure 1.
Figure 1. Schematics showing the binding mode of ligands to protein kinases. (a) ATP. (b) Purvalanol B in CDK2 (PDB code 1CKP). (c) NU2058 in CDK2 (PDB code 1E1V). Hydrogen bonds are indicated by broken lines.

Figure 5.
Figure 5. Key elements for the hydrogen-bonding pattern of an ATP-mimetic compound. The orientation of R3-O of the group A kinase is more favorable for that of the group B kinase because of the difference in the length of the specificity linker.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 73, 795-801) copyright 2008.

Figures were selected by an automated process.