Master's Program in Biology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-0821, Japan.
Doctoral Program in Biology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-0821, Japan.
J Phys Chem B. 2024 Nov 7;128(44):10823-10830. doi: 10.1021/acs.jpcb.4c05191. Epub 2024 Oct 23.
Enzymatic activity is regulated by various mechanisms to ensure biologically proper functions. Notable instances of such regulation in homodimeric enzymes include "all-of-the-sites activity" and "half-of-the-sites activity". The difference in these activities lies in whether one or both of the subunits are simultaneously active. Owing to its uniqueness, the mechanism of half-of-the-sites activity has been widely investigated. Consequently, structural asymmetry derived from cooperative motion is considered to induce half-of-the-sites activity. In contrast, recent investigations have suggested that subunit-intrinsic properties or structural fluctuation also induces structural asymmetry. Hence, the mechanism underlying half-of-the-sites activity has not been completely elucidated. Additionally, most previous studies have focused only on half-of-the-sites activity. Therefore, by comparing the structural and dynamical properties of two representative homodimers exhibiting all-of-the-sites and half-of-the-sites activities, respectively, we attempted to elucidate the mechanism of half-of-the-sites activity. Specifically, all-atom molecular dynamics simulations were applied to lysyl-tRNA synthetase and tyrosyl-tRNA synthetase. Our analysis revealed that structural fluctuation is sufficient to induce structural asymmetry in addition to the well-established factor of cooperative motion. Considering that structural fluctuation is a common characteristic of any enzyme, it could be a general factor in half-of-the-sites activity.
酶的活性受到多种机制的调节，以确保其具有适当的生物学功能。在同二聚体酶中，有许多这样的调节实例，包括“全位点活性”和“半位点活性”。这些活性的区别在于一个或两个亚基是否同时具有活性。由于其独特性，半位点活性的机制已被广泛研究。因此，协同运动产生的结构不对称性被认为会诱导半位点活性。相比之下，最近的研究表明，亚基内在性质或结构波动也会诱导结构不对称性。因此，半位点活性的机制尚未完全阐明。此外，大多数先前的研究仅关注半位点活性。因此，通过比较分别表现出全位点和半位点活性的两个代表性同二聚体的结构和动力学性质，我们试图阐明半位点活性的机制。具体来说，我们对赖氨酰-tRNA 合成酶和酪氨酸-tRNA 合成酶进行了全原子分子动力学模拟。我们的分析表明，结构波动除了协同运动这一公认因素之外，还足以诱导结构不对称性。考虑到结构波动是任何酶的共同特征，它可能是半位点活性的一个普遍因素。
