PDBsum entry 1agw

Protein kinase

PDB id: 1agw

Contents

Protein chains

278 a.a. *

Ligands

SU2 ×2

Waters ×234

* Residue conservation analysis

PDB id:

1agw

Name:

Protein kinase

Title:

Crystal structure of the tyrosine kinase domain of fibroblast growth factor receptor 1 in complex with su4984 inhibitor

Structure:

Fgf receptor 1. Chain: a, b. Fragment: tyrosine kinase domain. Synonym: fgfr1k. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf9. Organelle: cytoplasm. Cellular_location: cytoplasmic domain. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.40Å R-factor: 0.194 R-free: 0.280

Authors:

M.Mohammadi,J.Schlessinger,S.R.Hubbard

Key ref:

M.Mohammadi et al. (1997). Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science, 276, 955-960. PubMed id: 9139660 DOI: 10.1126/science.276.5314.955

Date:

25-Mar-97 Release date: 25-Mar-98

Protein chains

P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1 from Homo sapiens

Seq: 822 a.a.

Struc: 278 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: 10.1126/science.276.5314.955

Science 276:955-960 (1997)

PubMed id: 9139660

Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.

M.Mohammadi, G.McMahon, L.Sun, C.Tang, P.Hirth, B.K.Yeh, S.R.Hubbard, J.Schlessinger.

ABSTRACT

A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.

Selected figure(s)

Figure 3.
Fig. 3. 2F[o] F[c] electron density maps computed after simulated annnealing (1000 K) with the inhibitors omitted from the atomic models. Carbon atoms are colored yellow, oxygen atoms red, and nitrogen atoms blue. The red spheres represent water molecules. Maps are^ contoured at 1 . (A) Map of FGFR1K-SU4984 computed at 2.4^ Å resolution. (B) Map of FGFR1K-SU5402 computed at 2.5^ Å resolution. Figure prepared with SETOR (34).

Figure 5.
Fig. 5. Stereoviews of the inhibitor binding sites. The side chains of residues that interact with the inhibitors are shown. Carbon atoms of the inhibitor and FGFR1K are green and orange, respectively; oxygen atoms are red and nitrogen atoms are blue. Coloring of^ the backbone representation is the same as in Fig. 4. Selected^ hydrogen bonds are shown as black lines. (A) FGFR1K-SU4984. (B) FGFR1K-SU5402.

The above figures are reprinted by permission from the AAAs: Science (1997, 276, 955-960) copyright 1997.

Figures were selected by an automated process.