3-磷酸甘油醛脱氢酶（GAPDH）中潜在有害突变集合的结构，功能和稳定性分析，用于早期检测到LUAD
Structure, function and stability analysis on potential deleterious mutation ensemble in glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for early detection of LUAD
影响因子:5.10000
分区:医学3区 / 药学2区 医学：研究与实验3区
发表日期:2024 Dec 01
作者:
Pearl John, C Sudandiradoss
摘要
肺腺癌（LUAD）是肺癌中最突出的组织学亚型，这是癌症死亡率的主要原因。高突变和糖酵解率是肺癌的主要报道改变。在我们的研究中，我们阐明了关键的糖酵解酶甘油醛的结构和功能作用3-磷酸盐脱氢酶（GAPDH）和相关的SNP在LUAD进展中的基因表达分析揭示了LUAD中GAPDH的高表达。在计算机工具和分析中，用于识别和表征有害SNP。分子对接和动力学模拟（MDS）的研究表征了优先级有害突变的结构后果。基于序列的GAPDH中的序列分析导致28个有害SNP，其中6个SNP显示出有害和破坏性效果。基于结构的分析导致了2个稳定的RS IDS RS11549328（D39Y）和RS200102749（S51Y）的SNP。 GAPDH序列的IDR和PTM分析导致IDR区域从191到194个位置，IDR得分为0.511、0.520、0.517和0.503，并进行了PTM修改。已确定的有害SNP（D39Y和S51Y）在功能和保存的gapdh的功能和保存域中落在。此外，GAPDH的IDR区域内的PTM存在可能有助于其在LUAD中增强的糖酵解活性。我们研究的结果为LUAD进展中GAPDH的病理方面提供了潜在的背景有害突变体。
Abstract
Lung adenocarcinoma (LUAD) is the most prominent histological subtype among the lung cancer which is a leading cause in the cancer mortality rate. High mutational and glycolytic rates are the major reported alterations in the lung cancer. Here in our study we are elucidating the structural and functional role of key glycolytic enzyme Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and associated SNPs in LUAD progression.Our gene expression analysis reveals high expression of GAPDH in the LUAD. In silico tools and analysis were used for the identification and characterization of the deleterious SNPs. Molecular Docking and dynamics simulations (MDS) studies characterized the structural consequences of prioritized deleterious mutations.The sequence based analysis to identify SNPs in GAPDH resulted in 28 deleterious SNPs and 6 SNPs among them showed deleterious and damaging effect. The structural based analysis resulted in 2 stabilizing SNPs of rs ids rs11549328 (D39Y) and rs200102749 (S51Y) in the conserved domain. The IDR and PTM analysis of the GAPDH sequence resulted an IDR region from 191 to 194 positions with an IDR score of 0.511, 0.520, 0.517 and 0.503 with the PTM modifications.The identified deleterious SNPs (D39Y and S51Y) fall in the functional and conserved domain of GAPDH. In addition, the existence of PTMs within the IDR region of the GAPDH may contribute to its enhanced glycolytic activity in LUAD. The results of our study provide potential background deleterious mutants the pathological aspect of GAPDH in LUAD progression.