在人 FOLH1 基因中非同义单核酸多态的非同义单核酸多态结构和功能分析
Abtin Tondar1,2, Muhammad Irfan3, Sergio Sánchez-Herrero1
1Department of Computer Science, Multimedia and Telecommunication, Interuniversity Doctoral Program in Bioinformatics, Universitat Oberta de Catalunya, Barcelona (UOC), Spain.
In silico pharmacology
|February 28, 2025
概括
这项研究确定了FOLH1基因中的三个关键非同义单核酸多态 (nsSNP),这些多态影响前列腺特异性膜抗原 (PSMA) 的结构和功能,为前列腺癌的发展提供了洞察力.
科学领域:
- 遗传学 遗传学 是一个
- 生物化学 生化学
- 计算生物学 计算生物学
背景情况:
- 非同义单核酸多态 (nsSNP) 可以改变蛋白质功能并影响疾病易感性.
- 叶酸酸酶1 (FOLH1) 基因编码前列腺特异性膜抗原 (PSMA),这是一个涉及前列腺癌的蛋白质.
研究的目的:
- 进行FOLH1基因中nsSNP的in-silico分析,以了解它们对PSMA蛋白的结构和功能影响.
- 在FOLH1中识别致病性nsSNP并评估它们对前列腺癌的潜在影响.
主要方法:
- 从数据库中检索了504个SNP,并使用5个in-silico工具过以识别15个潜在的致病性nsSNP.
- 利用MutPred2预测结构/功能变化和I-Mutant 2.0进行蛋白质稳定性分析.
- 使用ConSurf进行保护分析和分析后翻译修改 (PTM).
主要成果:
- 确定了15种致病性nsSNP,其中R255H,R255C和G168E始终被预测为致病性.
- 观察到PSMA蛋白质结构的显著变化,包括螺旋内容,糖化和跨膜性质的变化.
- 发现大多数nsSNP的蛋白质稳定性下降,除了G168E,并确定了R255H和R255C变体中的糖化位的损失.
结论:
- 在分析对于了解FOLH1 nsSNP对PSMA的功能影响至关重要.
- 致病性nsSNP,特别是R255H和R255C,可能会通过改变稳定性和糖化来影响PSMA功能,可能会影响前列腺癌.
- 这些发现有助于了解nsSNP在前列腺癌病原和耐药性中的作用.
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