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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Alpha7 helix plays an important role in the conformational stability of PTP1B.
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Alpha7 helix plays an important role in the conformational stability of PTP1B.

机译：Alpha7螺旋在PTP1B的构象稳定性中起重要作用。

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摘要

The C-terminus of Protein Tyrosine Phosphatase 1B (PTP1B) includes an alpha-helix alpha7), which forms an allosteric binding site 20 a away from the active site. This helix is specific to PTP1B and its truncation decreases the catalytic activity significantly. Here, molecular dynamics (MD) simulations in the presence and absence of alpha7 were performed to investigate the role played by alpha7. The highly mobile alpha7 was found to maintain its contacts with loop 11 (L11)alpha3 helix throughout the simulations. The interactions of Tyr152 on L11, Tyr176, Thr177 on the catalytically important WPD loop and Ser190 on alpha3 are important for the conformational stability and the concerted motions of the regions surrounding the WPD loop. In the absence of alpha7, L11 and WPD loop move away from their crystal structure conformations, resulting in the loss of the interactions in this region, and a decrease in the residue displacement correlations in the vicinity of WPD loop. Therefore, we suggest that one of the functionally important roles of alpha7 may be to limit the L11 and alpha3 motions, and, facilitate the WPD loop motions. Truncation of alpha7 in PTP1B is found to affect distant regions as well, such as the substrate recognition site and the phosphate binding-loop (P-loop), changing the conformations of these regions significantly. Our results show that the PTP1B specific alpha7 is important for the conformation and dynamics of the WPD loop, and also may play a role in ligand binding.
机译：蛋白酪氨酸磷酸酶1B（PTP1B）的C末端包括一个α-螺旋α7，它形成一个远离活性位点的变构结合位点20a。该螺旋是PTP1B特有的，其截短会大大降低催化活性。在这里，在存在和不存在alpha7的情况下进行分子动力学（MD）模拟，以研究alpha7发挥的作用。在整个模拟过程中，发现高度移动的alpha7保持与回路11（L11）alpha3螺旋的接触。 L11上的Tyr152，催化上重要的WPD环上的Tyr176，Thr177和alpha3上的Ser190的相互作用对于构象稳定性和WPD环周围区域的协调运动很重要。在没有alpha7的情况下，L11和WPD环会偏离其晶体结构构象，从而导致该区域中相互作用的丧失，并且WPD环附近的残基位移相关性会降低。因此，我们建议alpha7的功能上重要的作用之一可能是限制L11和alpha3的运动，并促进WPD循环运动。发现PTP1B中的alpha7截短也影响远距离区域，例如底物识别位点和磷酸盐结合环（P环），从而显着改变了这些区域的构象。我们的结果表明，PTP1B特异性alpha7对WPD环的构象和动力学很重要，并且可能在配体结合中起作用。

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