PDBsum entry 3nw6

Transferase

PDB id

3nw6

Loading ...

Contents

			Protein chain

					301 a.a. *

			Ligands

					LGW

			Waters ×230

* Residue conservation analysis

PDB id:

3nw6

Links

Name:

Transferase

Title:

Crystal structure of insulin-like growth factor 1 receptor (igf-1r-wt) complex with a carbon-linked proline isostere inhibitor (11a)

Structure:

Insulin-like growth factor 1 receptor. Chain: a. Fragment: kinase domain (residues 982-1286). Synonym: insulin-like growth factor i receptor, igf-i receptor. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: igf1r. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469

Resolution:

2.20Å

R-factor:

0.184

R-free:

0.253

Authors:

J.S.Sack

Key ref:

A.J.Sampognaro et al. (2010). Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase. Bioorg Med Chem Lett, 20, 5027-5030. PubMed id: 20675137

Date:

09-Jul-10

Release date:

28-Jul-10

PROCHECK

	Headers

	References

Protein chain

P08069 (IGF1R_HUMAN) - Insulin-like growth factor 1 receptor from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:					1367 a.a. 301 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		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 20:5027-5030 (2010)
PubMed id: 20675137

Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase.
A.J.Sampognaro, M.D.Wittman, J.M.Carboni, C.Chang, A.F.Greer, W.W.Hurlburt, J.S.Sack, D.M.Vyas.

ABSTRACT

Pyrrolidine, pyrrolidinone, carbocyclic, and acyclic groups were used as isosteric proline replacements in a series of insulin-like growth factor I receptor kinase/insulin receptor kinase inhibitors. Examples that were similar in potency to proline-containing reference compounds were shown to project a key fluoropyridine amide into a common space, while less potent compounds were not able to do so for reasons of stereochemistry or structural rigidity.