PDBsum entry 3l8v

Transferase

PDB id

3l8v

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Contents

			Protein chain

					293 a.a. *

			Ligands

					L8V

			Waters ×100

* Residue conservation analysis

PDB id:

3l8v

Links

Name:

Transferase

Title:

Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a biarylamine based inhibitor

Structure:

Hepatocyte growth factor receptor. Chain: a. Fragment: tyrosine kinase domain, unp residues 1049-1360. Synonym: hgf receptor, scatter factor receptor, sf receptor, hgf/sf receptor, met proto-oncogene tyrosine kinase, c-met. Engineered: yes

Source:

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

Resolution:

2.40Å

R-factor:

0.185

R-free:

0.237

Authors:

J.Sack

Key ref:

D.K.Williams et al. (2010). Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors. Bioorg Med Chem Lett, 20, 2998-3002. PubMed id: 20382527

Date:

04-Jan-10

Release date:

05-May-10

PROCHECK

	Headers

	References

Protein chain

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

Seq: Struc:

Seq: Struc:

Seq: Struc:					1390 a.a. 293 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

	Bioorg Med Chem Lett 20:2998-3002 (2010)
PubMed id: 20382527

Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors.
D.K.Williams, X.T.Chen, C.Tarby, R.Kaltenbach, Z.W.Cai, J.S.Tokarski, Y.An, J.S.Sack, B.Wautlet, J.Gullo-Brown, B.J.Henley, R.Jeyaseelan, K.Kellar, V.Manne, G.L.Trainor, L.J.Lombardo, J.Fargnoli, R.M.Borzilleri.

ABSTRACT

Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21487786

J.Caballero, M.Quiliano, J.H.Alzate-Morales, M.Zimic, and E.Deharo (2011).
Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors.

J Comput Aided Mol Des, 25, 349-369.

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.