1DZC

High resolution structure of acidic fibroblast growth factor. Mutant FGF-4-ALA-(24-154), 24 NMR structures

1DZC の概要

• エントリーDOI: 10.2210/pdb1dzc/pdb
• 関連するPDBエントリー: 1AXM 1DZD 1RML 2AFG 2AXM
• 分子名称: FIBROBLAST GROWTH FACTOR 1 (1 entity in total)
• 機能のキーワード: growth factor, cell cycle, antitumoral
• 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: 1
• 化学式量合計: 14683.45

構造登録者

Lozano, R.M.,Pineda-Lucena, A.,Gonzalez, C.,Jimenez, M.A.,Cuevas, P.,Redondo-Horcajo, M.,Sanz, J.M.,Rico, M.,Gimenez-Gallego, G. (登録日: 2000-02-24, 公開日: 2000-03-16, 最終更新日: 2024-05-15)

主引用文献

Lozano, R.M.,Pineda-Lucena, A.,Gonzalez, C.,Jimenez, M.A.,Cuevas, P.,Redonde-Horcajo, M.,Sanz, J.M.,Rico, M.,Gimenez-Gallego, G.
1H-NMR Structural Characterization of a Non Mitogenic, Vasodilatory, Ischemia-Protector and Neuromodulatory Acidic Fibroblast Growth Factor
Biochemistry, 39:4982-, 2000

PubMed Abstract: A shortened genetically engineered form of acidic fibroblast growth factor (aFGF), that includes amino acids 28-154 of the full-length sequence (154 residues) plus Met in substitution of Leu27, does not induce cell division even though it is recognized by the cell membrane receptor, triggers the early mitogenic events, and retains the neuromodulatory, vasoactive, and cardio- and neuroprotective properties of the native full-length molecule. Taken together, these properties make this truncated aFGF a promising compound in the treatment of a wide assortment of neurological and cardiovascular pathologies where aFGF mitogenic activity is dispensable. Differences in biological activities between the shortened aFGF and the wild-type form have been attributed to lack of stability, and to the specific amino acid sequence missing at the N-terminus. Here we show that this shortened aFGF form has a three-dimensional structure even more stable than the wild-type protein at the mitogenic assay conditions; that this structure is similar to that of the wild type except at site 1 of interaction with the cell membrane receptor; that its lack of mitogenic activity cannot be attributed to the specific missing sequence; and that the vasodilatory activity of aFGF seems impaired by alterations of the three-dimensional structure of site 2 of interaction with the cell membrane receptor.

PubMed: 10819962
DOI: 10.1021/BI992544N

実験手法

SOLUTION NMR