XRAY STRUCTURE DETERMINATION OF RETINAL SPECIFIC DEHYDROGENASE

成纤维细胞生长因子家族由一个组组成 至少九种细胞因子的部分特征是结合 对肝素，在氨基酸水平上有30-55%的同源性。 FGFs与一系列受体结合，其中FGFR1包括 细胞内分裂酪氨酸部分、跨膜区和 由两个或三个Ig结构域组成的胞外区，D(I)，D (Ii)及D(Iii)。在成年生物体中，FGFs被认为扮演着 在Will愈合中的作用，在肿瘤生长的病理中，类风湿 关节炎、糖尿病视网膜病变和牛皮癣。新的拮抗剂 成纤维细胞生长因子/成纤维细胞生长因子1的相互作用有望在 血管生成和新生血管疾病状态的控制 肿瘤生长和转移等树突状脱落。为了进一步了解 D(II)结构域在结合机制中的核心作用 在成纤维细胞生长因子系统中，我们进行了蛋白质结晶和 FGFR1 118个残基片段的X射线衍射研究 在大肠杆菌中表达。虽然我们已经获得了x射线衍射数据 至~3使用存储荧光粉从~75 mm尺寸的晶体中进行分辨率 探测器和铜阳极源旋转，我们感觉到了 同步辐射和冷冻将提供更好的质量和 这些弱衍射晶体上的较高分辨率数据 天然蛋白质。反射的相位将由MIR完成 采用使用旋转阳极源收集的低分辨率数据。

The fibroblast growth factor (FGF) family is comprised of a group of at least nine cytokines which are characterized in part by binding to heparin, and which share 30-55% identity at the amino acid level. FGFs bind to a series of receptors among which is FGFR1 consisting of an intracellular split tyrosine portion, a transmembrane region, and an extracellular region comprised of two or three Ig domains, D(I), D (II), and D (III). In adult organisms, the FGFs are thought to play a role in would healing, in the pathology of tumor growth, rheumatoid arthritis, diabetic retinopathy, and psoriasis. New antagonists of FGF/FGFR1 interactions are expected to find applications for the control of angiogenesis and disease states that are neovascularization depdendent such as tumor growth and metastasis. To further understand the central role that the D(II) domain plays in the binding mechanism of the FGF system, we have undertaken a protein crystallization and x-ray diffraction study of this 118 residue fragment of FGFR1 expressed in E. coli. While we have obtained x-ray diffraction data to ~3
resolution from ~75 mm sized crystals using a storage phosphor detector and a Cu rotating anode source, we feel the combination of synchrotron radiation and cryocooling will give better quality and higher resolution data on these weakly diffracting crystals of the native protein. Phasing of the reflections will be done by MIR employing low resolution data collected using a rotating anode source.