Fanelli F
Dipartimento di Chimica, Universita di Modena e Reggio Emilia, Via Campi 183, Modena, 41100, Italy.
J Mol Biol. 2000 Mar 10;296(5):1333-51. doi: 10.1006/jmbi.2000.3516.
Here, three-dimensional model building and molecular dynamics simulations of the luteinizing hormone receptor have been employed to generate hypotheses about the molecular mechanisms underlying the activation of the receptor induced by naturally occurring activating mutations. The comparative analysis of the wild-type receptor and of 16 constitutively active or inactive mutants has been instrumental in inferring the structural/dynamic features which could characterize the inactive and the active forms of the receptor. These features have been also employed for predicting the functional behavior of new receptor mutants. The results of this study might provide a structural framework to interpret the pathological effects induced by mutations of the luteinizing hormone receptor. In addition, the proposed theoretical model could be useful for engineering new mutations or ligands able to modulate receptor function.
在此，已采用促黄体生成素受体的三维模型构建和分子动力学模拟，以生成关于由天然存在的激活突变诱导的受体激活背后分子机制的假设。对野生型受体和16种组成型活性或非活性突变体的比较分析，有助于推断可表征受体非活性和活性形式的结构/动力学特征。这些特征也已用于预测新受体突变体的功能行为。本研究结果可能提供一个结构框架，以解释促黄体生成素受体突变所诱导的病理效应。此外，所提出的理论模型可能有助于设计能够调节受体功能的新突变或配体。
