PDBsum entry 7b3v

Transferase

PDB id: 7b3v

Contents

Protein chain

274 a.a.

Ligands

SWB

Waters ×222

PDB id:

7b3v

Name:

Transferase

Title:

Crystal structure of c-met bound by compound 3

Structure:

Hepatocyte growth factor receptor. Chain: a. Synonym: hgf receptor,hgf/sf receptor,proto-oncogenE C-met,scatter factor receptor,sf receptor,tyrosine-protein kinase met. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: met. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.93Å R-factor: 0.226 R-free: 0.248

Authors:

G.W.Collie

Key ref:

G.W.Collie et al. (2021). Structural Basis for Targeting the Folded P-Loop Conformation of c-MET. ACS Med Chem Lett, 12, 162-167. PubMed id: 33488978 DOI: 10.1021/acsmedchemlett.0c00392

Date:

01-Dec-20 Release date: 09-Dec-20

Protein chain

P08581  (MET_HUMAN) -  Hepatocyte growth factor receptor from Homo sapiens

Seq: 1390 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

DOI no: 10.1021/acsmedchemlett.0c00392

ACS Med Chem Lett 12:162-167 (2021)

PubMed id: 33488978

Structural Basis for Targeting the Folded P-Loop Conformation of c-MET.

G.W.Collie, I.N.Michaelides, K.Embrey, C.J.Stubbs, U.Börjesson, I.L.Dale, A.Snijder, L.Barlind, K.Song, P.Khurana, C.Phillips, R.I.Storer.

ABSTRACT

We report here a fragment screen directed toward the c-MET kinase from which we discovered a series of inhibitors able to bind to a rare conformation of the protein in which the P-loop adopts a collapsed, or folded, arrangement. Preliminary SAR exploration led to an inhibitor (7) with nanomolar biochemical activity against c-MET and promising cell activity and kinase selectivity. These findings increase our structural understanding of the folded P-loop conformation of c-MET and provide a sound structural and chemical basis for further investigation of this underexplored yet potentially therapeutically exploitable conformational state.