3K1X

Acidic Fibroblast Growth Factor (FGF-1) complexed with dobesilate

3K1X の概要

• エントリーDOI: 10.2210/pdb3k1x/pdb
• 関連するPDBエントリー: 3JUT
• 分子名称: Heparin-binding growth factor 1, 2,5-dihydroxybenzenesulfonic acid (3 entities in total)
• 機能のキーワード: acidic fibroblast growth factor, inhibitors, acetylation, hormone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P05230
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 88896.57

構造登録者

Romero, A.,Fernandez, I.S.,Gimenez-Gallego, G. (登録日: 2009-09-29, 公開日: 2010-02-02, 最終更新日: 2023-11-01)

主引用文献

Fernandez, I.S.,Cuevas, P.,Angulo, J.,Lopez-Navajas, P.,Canales-Mayordomo, A.,Gonzalez-Corrochano, R.,Lozano, R.M.,Valverde, S.,Jimenez-Barbero, J.,Romero, A.,Gimenez-Gallego, G.
Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors.
J.Biol.Chem., 285:11714-11729, 2010

PubMed Abstract: Fibroblast growth factors are key proteins in many intercellular signaling networks. They normally remain attached to the extracellular matrix, which confers on them a considerable stability. The unrestrained accumulation of fibroblast growth factors in the extracellular milieu, either due to uncontrolled synthesis or enzymatic release, contributes to the pathology of many diseases. Consequently, the neutralization of improperly mobilized fibroblast growth factors is of clear therapeutic interest. In pursuing described rules to identify potential inhibitors of these proteins, gentisic acid, a plant pest-controlling compound, an aspirin and vegetarian diet common catabolite, and a component of many traditional liquors and herbal remedies, was singled out as a powerful inhibitor of fibroblast growth factors. Gentisic acid was used as a lead to identify additional compounds with better inhibitory characteristics generating a new chemical class of fibroblast growth factor inhibitors that includes the agent responsible for alkaptonuria. Through low and high resolution approaches, using representative members of the fibroblast growth factor family and their cell receptors, it was shown that this class of inhibitors may employ two different mechanisms to interfere with the assembly of the signaling complexes that trigger fibroblast growth factor-driven mitogenesis. In addition, we obtained evidence from in vivo disease models that this group of inhibitors may be of interest to treat cancer and angiogenesis-dependent diseases.

PubMed: 20145243
DOI: 10.1074/jbc.M109.064618

実験手法

X-RAY DIFFRACTION (1.98 Å)