PDBsum entry 3lco

Transferase

PDB id: 3lco

Contents

Protein chain

293 a.a. *

Ligands

LC0

* Residue conservation analysis

PDB id:

3lco

Name:

Transferase

Title:

Inhibitor bound to a dfg-out structure of the kinase domain of csf-1r

Structure:

Macrophage colony-stimulating factor 1 receptor. Chain: a. Fragment: kinase domain. Synonym: csf-1-r, proto-oncogenE C-fms. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: csf-1r, csf1r, fms. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

3.40Å R-factor: 0.247 R-free: 0.289

Authors:

S.Kamtekar,J.E.Day,B.A.Reitz,K.J.Mathis,M.J.Meyers

Key ref:

M.J.Meyers et al. (2010). Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode. Bioorg Med Chem Lett, 20, 1543-1547. PubMed id: 20137931

Date:

11-Jan-10 Release date: 15-Sep-10

Protein chain

P07333  (CSF1R_HUMAN) -  Macrophage colony-stimulating factor 1 receptor from Homo sapiens

Seq: 972 a.a.

Struc: 293 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

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

Bioorg Med Chem Lett 20:1543-1547 (2010)

PubMed id: 20137931

Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode.

M.J.Meyers, M.Pelc, S.Kamtekar, J.Day, G.I.Poda, M.K.Hall, M.L.Michener, B.A.Reitz, K.J.Mathis, B.S.Pierce, M.D.Parikh, D.A.Mischke, S.A.Long, J.J.Parlow, D.R.Anderson, A.Thorarensen.

ABSTRACT

The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.