Lee Jihun, Blaber Sachiko I, Irsigler Andre, Aspinwall Eric, Blaber Michael
Department of Biomedical Sciences, Florida State University, Tallahassee, 32306-4300, USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Nov 1;65(Pt 11):1097-104. doi: 10.1107/S1744309109040287. Epub 2009 Oct 30.
The rabbit is an important and de facto animal model in the study of ischemic disease and angiogenic therapy. Additionally, fibroblast growth factor 1 (FGF-1) is emerging as one of the most important growth factors for novel proangiogenic and pro-arteriogenic therapy. However, despite its significance, the fundamental biophysical properties of rabbit FGF-1, including its X-ray structure, have never been reported. Here, the cloning, crystallization, X-ray structure and determination of the biophysical properties of rabbit FGF-1 are described. The X-ray structure shows that the amino-acid differences between human and rabbit FGF-1 are solvent-exposed and therefore potentially immunogenic, while the biophysical studies identify differences in thermostability and receptor-binding affinity that distinguish rabbit FGF-1 from human FGF-1.
兔子是缺血性疾病和血管生成治疗研究中一种重要且事实上的动物模型。此外，成纤维细胞生长因子1（FGF-1）正成为新型促血管生成和促动脉生成治疗中最重要的生长因子之一。然而，尽管其具有重要意义，但兔FGF-1的基本生物物理特性，包括其X射线结构，从未被报道过。在此，描述了兔FGF-1的克隆、结晶、X射线结构以及生物物理特性的测定。X射线结构表明，人和兔FGF-1之间的氨基酸差异是暴露于溶剂中的，因此可能具有免疫原性，而生物物理研究确定了热稳定性和受体结合亲和力方面的差异，这些差异将兔FGF-1与人类FGF-1区分开来。
