PDBsum entry: 1rml

Growth factor

PDB id: 1rml

Contents

Protein chain

131 a.a. *

Ligands

NTS

* Residue conservation analysis

PDB id:

1rml

Name:

Growth factor

Title:

Nmr study of acid fibroblast growth factor bound to 1,3,6- naphthalene trisulphonate, 26 structures

Structure:

Acidic fibroblast growth factor. Chain: a. Fragment: residues 23 - 154. Synonym: heparin-binding growth factor 1. Engineered: yes

Source:

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

NMR struc:

26 models

Authors:

R.M.Lozano,M.A.Jimenez,J.Santoro,M.Rico,G.Gimenez-Gallego

Key ref:

R.M.Lozano et al. (1998). Solution structure of acidic fibroblast growth factor bound to 1,3, 6-naphthalenetrisulfonate: a minimal model for the anti-tumoral action of suramins and suradistas. J Mol Biol, 281, 899-915. PubMed id: 9719643 DOI: 10.1006/jmbi.1998.1977

Date:

21-May-98 Release date: 11-Nov-98

Protein chain

P05230  (FGF1_HUMAN) -  Heparin-binding growth factor 1

Seq: 155 a.a.

Struc: 131 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (8 terms)
• Biological process: multicellular organismal development (22 terms)
• Biochemical function: protein binding (6 terms)

DOI no: 10.1006/jmbi.1998.1977

J Mol Biol 281:899-915 (1998)

PubMed id: 9719643

Solution structure of acidic fibroblast growth factor bound to 1,3, 6-naphthalenetrisulfonate: a minimal model for the anti-tumoral action of suramins and suradistas.

R.M.Lozano, M.Jiménez, J.Santoro, M.Rico, G.Giménez-Gallego.

ABSTRACT

Recent data show that anti-angiogenesis may provide a promising route to treat cancer. Fibroblast growth factors (FGFs) are powerful angiogenic polypeptides, whose mitogenic activity requires the presence of heparin-like compounds. It has been shown that angiogenesis promoted by FGFs on inhibition by monoclonal antibodies and antisense targeting can also inhibit tumour growth. Derivatives of suramin, a polysulfonated binaphthyl urea and binaphthylsulfonated derivatives of distamycin, suradistas, constitute an important group of potential anti-cancer agents. These compounds compete with heparin in forming tight complexes with FGFs. This inhibits the recognition of these growth factors by their tyrosine kinase membrane receptors thereby suppressing their angiogenic activity. Here we show that 1,3,6-naphthalenetrisulfonate, a common chemical function of the suramins and suradistas with the highest anti-angiogenic activity inhibits the mitogenic activity of acidic fibroblast growth factor, and that this inhibition is relieved by increasing concentrations of heparin in the assay. We have also solved the three-dimensional structure in solution of the protein complexed to this compound. The structural data provide clues that may help in understanding the inhibitory effect of suramins and suradistas, and could contribute to the development of new anti-tumoral drugs.

Selected figure(s)

Figure 4.
Figure 4. Differences in d-values between the NH amide (A) and C^aH (B) protons for each residue in NTS and MIHS-bound aFGF.

Figure 9.
Figure 9. Surface of the mean structures of NTS (left) and MIHS-bound (right) aFGF color mapped with the electrostatic potential (red, negative; blue, positive), showing the residues, highlighted in Figure 8, that presumably interact with the tyrosine kinase cell membrane receptors. Residues whose interaction is suggested by visual inspection of the region defined by the ones identified by point-directed mutagenesis (green color in Figure 8) are labelled with an asterisk (*).

The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 281, 899-915) copyright 1998.

Figures were selected by an automated process.