Prodromou C, Roe S M, O'Brien R, Ladbury J E, Piper P W, Pearl L H
Department of Biochemistry and Molecular Biology, University College London, United Kingdom.
Cell. 1997 Jul 11;90(1):65-75. doi: 10.1016/s0092-8674(00)80314-1.
Hsp90 molecular chaperones in eukaryotic cells play essential roles in the folding and activation of a range of client proteins involved in cell cycle regulation, steroid hormone responsiveness, and signal transduction. The biochemical mechanism of Hsp90 is poorly understood, and the involvement of ATP in particular is controversial. Crystal structures of complexes between the N-terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a specific adenine nucleotide binding site homologous to the ATP-binding site of DNA gyrase B. This site is the same as that identified for the antitumor agent geldanamycin, suggesting that geldanamycin acts by blocking the binding of nucleotides to Hsp90 and not the binding of incompletely folded client polypeptides as previously suggested. These results finally resolve the question of the direct involvement of ATP in Hsp90 function.
真核细胞中的热休克蛋白90（Hsp90）分子伴侣在一系列参与细胞周期调控、类固醇激素反应和信号转导的客户蛋白的折叠和激活过程中发挥着重要作用。Hsp90的生化机制目前了解甚少，尤其是ATP在其中的作用存在争议。酵母Hsp90伴侣蛋白N端结构域与ADP/ATP复合物的晶体结构明确鉴定出一个与DNA促旋酶B的ATP结合位点同源的特定腺嘌呤核苷酸结合位点。该位点与抗肿瘤药物格尔德霉素所作用的位点相同，这表明格尔德霉素的作用机制是通过阻断核苷酸与Hsp90的结合，而不是像之前所认为的那样阻断未完全折叠的客户多肽的结合。这些结果最终解决了ATP是否直接参与Hsp90功能的问题。
