NUCLEOTIDE DEPENDENT MOVEMENTS OF KINESIN MOTOR DOMAIN: SIMULATED ANNEALING

三磷酸腺苷结合的运动域的结构已经被 相对于已知的预测和构象差异 确定了该蛋白的ADP结合形式，*如文献[1]中报道的 参考文献[96]。这种差异应该归因于 产生力量的三磷酸腺苷水解酶。候选的ATP-Kinesin结构是 通过模拟退火法获得，通过放置ATP ADP-激动素晶体结构中的伽马-磷酸，并通过 原子间距离约束。这种约束的选择是 根据突变实验，Gly234是一种 伽马-磷酸盐敏感残留物以及结构 激动素与同源NCD马达和G 蛋白质。核苷酸依赖的构象预测 差异揭示了核苷酸之间的变构偶联 口袋和动蛋白的微管结合部位。的交互作用 带有Gly234和Ser202的三磷酸腺苷触发马达的结构变化 结构域，作为激动素的变构修饰物的核苷酸 微管结合状态。我们建议在有ATP存在的情况下 激动素推测的微管结合区(L8、L12、L11、α4、 字母5和字母6)形成形状互补的脸 微管表面。在ADP存在下，微管结合 相对于ATP结合形式，脸部采用更加凸起的形状， 降低动蛋白与微管的亲和力。

The structure of an ATP-bound kinesin motor domain has been predicted and conformational differences relative to the known ADP-bound form of the protein were identified,* as reported in reference [96]. The differences should be attributed to force-producing ATP hydrolysis. Candidate ATP-kinesin structures were obtained by simulated annealing, by placement of the ATP gamma-phosphate in the crystal structure of ADP-kinesin, and by inter-atomic distance constraints. The choice of such constraints was based on mutagenesis experiments, which identified Gly234 as one of the gamma-phosphate sensing residues, as well as on structural comparison of kinesin with the homologous ncd motor and with G proteins. The prediction of nucleotide-dependent conformational differences reveals an allosteric coupling between the nucleotide pocket and the microtubule binding site of kinesin. Interactions of ATP with Gly234 and Ser202 trigger structural changes in the motor domain, the nucleotide acting as an allosteric modifier of kinesin's microtubule-binding state. We suggest that in the presence of ATP kinesin's putative microtubule binding regions (L8, L12, L11, alpha4, alpha5 and alpha6) form a face complementary in shape to the microtubule surface. In the presence of ADP, the microtubule binding face adopts a more convex shape relative to the ATP-bound form, reducing kinesin's affinity to the microtubule.