1HKN

A complex between acidic fibroblast growth factor and 5-amino-2-naphthalenesulfonate

Summary for 1HKN

• Entry DOI: 10.2210/pdb1hkn/pdb
• Related: 1AXM 1DJS 1DZC 1DZD 1E0O 1EVT 1JQZ 1JT3 1JT4 1JT5 1JT7 1JTC 1K5U 1K5V 1QCT 1RML 2AFG 2AXM
• Descriptor: HEPARIN-BINDING GROWTH FACTOR 1, 5-AMINO-NAPHTALENE-2-MONOSULFONATE (3 entities in total)
• Functional Keywords: growth factor, mitogen, angiogenesis, heparin-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 6
• Total formula weight: 94710.64

Authors

Fernandez-Tornero, C.,Lozano, R.M.,Gimenez-Gallego, G.,Romero, A. (deposition date: 2003-03-10, release date: 2004-03-11, Last modification date: 2023-12-13)

Primary citation

Fernandez-Tornero, C.,Lozano, R.M.,Redondo-Horcajo, M.,Gomez, A.,Lopez, J.,Quesada, E.,Uriel, C.,Valverde, S.,Cuevas, P.,Romero, A.,Gimenez-Gallego, G.
Leads for Development of New Naphthalenesulfonate Derivatives with Enhanced Antiangiogenic Activity: Crystal Structure of Acidic Fibroblast Growth Factor in Complex with 5-Amino-2-Naphthalenesulfonate
J.Biol.Chem., 278:21774-, 2003

PubMed Abstract: Inhibition of angiogenesis-promoting factors such as fibroblast growth factors is considered to be a potential procedure for inhibiting solid tumor growth. Although several peptide-based inhibitors are currently under study, the development of antiangiogenic compounds of small molecular size is a pharmacological goal of considerable interest. We have already shown that certain naphthalene sulfonates constitute minimal functional substitutes of the antiangiogenic compounds of the suramin and suradista family. Using those data as a lead, we have carried out a rational search for new angiogenesis inhibitors that could provide new pharmacological insights for the development of antiangiogenic treatments. The results of the study strongly underline the relevance of the stereochemistry for an efficient inhibition of acidic fibroblast growth factor mitogenic activity by the naphthalene sulfonate family and allow us to formulate rules to aid in searching for new inhibitors and pharmaceutical developments. To provide further leads for such developments and acquire a detailed insight into the basis of the inhibitory activity of the naphthalene sulfonate derivatives, we solved the three-dimensional structure of acidic fibroblast growth factor complexed to 5-amino-2-naphthalenesulfonate, the most pharmacologically promising of the identified inhibitors. The structure shows that binding of this compound would hamper the interaction of acidic fibroblast growth factor with the different components of the cell membrane mitogenesis-triggering complex.

PubMed: 12676958
DOI: 10.1074/JBC.M212833200

Experimental method

X-RAY DIFFRACTION (2 Å)