Wittinghofer F
Max-Planck-Institut für medizinische Forschung, Abteilung Biophysik, Heidelberg, Germany.
Semin Cancer Biol. 1992 Aug;3(4):189-98.
The three-dimensional structure of the H-ras oncogene product p21 has been determined in both its active, GTP-bound and its inactive, GDP-bound forms. This has supplied a wealth of information on the mode of binding of guanine nucleotides, on the mechanism of the GTPase reaction and on the conformational change of the protein which accompanies GTP hydrolysis. The structural analysis has also given clues to the interaction of p21 with the regulatory proteins GAP (GTPase Activating Protein) and nucleotide exchange factor. The three-dimensional structures of oncogenic mutants of p21 have also been determined and can nicely explain different biochemical and biological behaviour of these mutant proteins.
H-ras癌基因产物p21的三维结构已在其活性的、结合GTP的形式以及非活性的、结合GDP的形式中被确定。这提供了大量关于鸟嘌呤核苷酸结合模式、GTPase反应机制以及伴随GTP水解的蛋白质构象变化的信息。结构分析也为p21与调节蛋白GAP(GTPase激活蛋白)和核苷酸交换因子的相互作用提供了线索。p21致癌突变体的三维结构也已被确定,并且可以很好地解释这些突变蛋白不同的生化和生物学行为。