PDBsum entry 5j9y

Transferase

PDB id

5j9y

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Contents

			Protein chain

					300 a.a.

			Ligands

					6HL

			Waters ×12

PDB id:

5j9y

Links

Name:

Transferase

Title:

Egfr-t790m in complex with pyrazolopyrimidine inhibitor 1b

Structure:

Epidermal growth factor receptor. Chain: a. Synonym: proto-oncogenE C-erbb-1,receptor tyrosine-protein kinase erbb-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: egfr, erbb, erbb1, her1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.80Å

R-factor:

0.185

R-free:

0.238

Authors:

C.Becker,J.Engel,D.Rauh

Key ref:

J.Engel et al. (2016). Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR. Angew Chem Int Ed Engl, 55, 10909-10912. PubMed id: 27496389 DOI: 10.1002/anie.201605011

Date:

11-Apr-16

Release date:

17-Aug-16

PROCHECK

	Headers

	References

Protein chain

P00533 (EGFR_HUMAN) - Epidermal growth factor receptor from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:					1210 a.a. 300 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* 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.

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

Reaction:

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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/anie.201605011	Angew Chem Int Ed Engl 55:10909-10912 (2016)
PubMed id: 27496389

Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR.
J.Engel, C.Becker, J.Lategahn, M.Keul, J.Ketzer, T.Mühlenberg, L.Kollipara, C.Schultz-Fademrecht, R.P.Zahedi, S.Bauer, D.Rauh.

ABSTRACT

Targeting acquired drug resistance represents the major challenge in the treatment of EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we describe the structure-based design, synthesis, and biological evaluation of a novel class of covalent EGFR inhibitors that exhibit excellent inhibition of EGFR-mutant drug-resistant cells. Protein X-ray crystallography combined with detailed kinetic studies led to a deeper understanding of the mode of inhibition of EGFR-T790M and provided insight into the key principles for effective inhibition of the recently discovered tertiary mutation at EGFR-C797S.