OBJECTIVE: To investigate the structural and functional implications of the TP53: 799C > T, p. (Arg267Trp) missense mutation, initially identified in a Saudi family, and understand its impact on TP53 functionality and related intermolecular interactions.
METHODS: Computational analyses were conducted to examine the structural modifications resulting from the TP53: 799C > T, p. (Arg267Trp) mutation. These analyses focused on the mutation\'s impact on hydrogen bonding, ionic interactions, and the specific interaction with Cell Cycle and Apoptosis Regulator 2 (CCAR2), as annotated in UniProt.
RESULTS: The study revealed that the native Arg267 residue is critical for a salt bridge interaction with glutamic acid at position 258. The mutation-induced charge alteration has the potential to disrupt this ionic bonding. Additionally, the mutation is located within an amino acid region crucial for interaction with CCAR2. The altered properties of the amino acid within this domain may affect its functionality and disrupt this interaction, thereby impacting the regulation of catalytic enzyme activity.
CONCLUSIONS: Our findings highlight the intricate intermolecular interactions governing TP53 functionality. The TP53: 799C > T, p. (Arg267Trp) mutation causes structural modifications that potentially disrupt critical ionic bonds and protein interactions, offering valuable insights for the development of targeted mutants with distinct functional attributes. These insights could inform therapeutic strategies for conditions associated with TP53 mutations.
目的:为了研究TP53:799C>T的结构和功能含义,p.(Arg267Trp)错义突变,最初是在一个沙特家庭,并了解其对TP53功能和相关分子间相互作用的影响。
方法:进行计算分析以检查TP53:799C>T产生的结构修饰,p.(Arg267Trp)突变。这些分析集中在突变对氢键的影响,离子相互作用,以及与细胞周期和凋亡调节因子2(CCAR2)的特异性相互作用,如UniProt中注释的。
结果:研究表明,天然的Arg267残基对于与位置258的谷氨酸的盐桥相互作用至关重要。突变诱导的电荷改变具有破坏该离子键合的潜力。此外,突变位于与CCAR2相互作用的关键氨基酸区域内。该结构域内氨基酸的性质改变可能会影响其功能并破坏这种相互作用,从而影响催化酶活性的调节。
结论:我们的发现强调了控制TP53功能的复杂分子间相互作用。TP53:799C>T,p。(Arg267Trp)突变会导致结构修饰,从而可能破坏关键的离子键和蛋白质相互作用,为开发具有不同功能属性的目标突变体提供有价值的见解。这些见解可以为与TP53突变相关的疾病提供治疗策略。