《生物化学Biochemistry》双语课件 01 绪论.ppt

Gtt2的晶体 Apo-form 2.2埃 GTS-bound form 磺化谷胱甘肽，2.2埃 GSH-bound form 谷胱甘肽，2.1埃 Gtt2的结构 溶液中为稳定二体，依靠静电和疏水作用力维持 每个单体含有两个结构域，N端Trx-like和C端全螺旋结构域 1980s and early 1990s Wonderful time for Molecular Biology Human Genome Project (1988-) Central Dogma (Crick F. 1958) Molecular Biology Omics: Metabolomics Transcriptomics Proteomics Structural Genomics (1998-) Genomics The era of Omics: (1998-2003 or later?) Omics = Oh! Mix! (millennium chaos?) What is Structural Genomics? It is an approach aiming at solving 3-D structures of the proteins encoded by an entire genome. Kim SH. Nature Structural Biology 1998 Original goals of SG: 1, to establish a catalogue/library of all folds covering the entire protein universe 2, to help the annotation of sequenced genomes International Structural Genomics Projects USA and Canada: (1998-) 9 NIH Structural Genomics Centers EU: France (3 centers: Paris-Sud, Marseille, Strasbourg) Germany (Structural Genomics Factory) UK (2 centers) (SPINE:Structural Proteomics in Europe, 2001-) Asia: Japan (RIKEN …) China (Yun-Yu SHI; Zihe RAO …) (2002-) Korea: Israel: Weizmann Structural Proteomics Center Flow chart: 1, Targets selection: Bioinformatics 2, PCR and cloning: Molecular Biology 3, Protein production: Biochemistry 4, Data collection (X-ray diffraction/NMR) 5,Structure determination: Structural Biology 6, Function interpretation: General Biology Core characteristics: High throughput (hundreds to thousands samples) Large-scale (milligram level of protein sample) Multi-discipline integration (from molecular biology to structural biology) high throughput parallelization (平行化) miniaturization (微量化) automation (自动化) cloning robot: 500-1000 clones /3 days crystallization robot: 96x3 drops/5 min protein sample for crystallization trials in nanoliter volumes (10nl) Hansen CL. et al. PNAS; 2002 Tag Size (aa) Application