XRAY STRUCTURE DETERMINATION OF RETINAL SPECIFIC DEHYDROGENASE

成纤维细胞生长因子（FGF）家族由以下组成： 至少9种细胞因子，其特征部分在于结合 肝素，并且在氨基酸水平上共享30-55%的同一性。 FGF结合一系列受体，其中FGFR 1由以下组成 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)和D（III）。 在成年生物体中，FGF被认为在体内发挥着重要作用。 在伤口愈合中的作用，在肿瘤生长的病理学中，类风湿性关节炎 关节炎、糖尿病视网膜病变和牛皮癣。 的新拮抗剂 FGF/FGFR 1的相互作用有望应用于 控制血管生成和新血管形成的疾病状态 依赖于肿瘤的生长和转移。 进一步了解 D（II）结构域在结合机制中发挥的核心作用 在FGF系统中，我们进行了蛋白质结晶， FGFR 1的这一118个残基片段的X射线衍射研究 在大肠杆菌中表达杆菌 虽然我们已经获得了x射线衍射数据， 至~3
使用存储磷光体从~75 mm尺寸晶体获得的分辨率 探测器和铜旋转阳极源，我们觉得结合 同步辐射和低温冷却将提供更好的质量， 这些弱衍射晶体的高分辨率数据 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.