甘氨基基转移酶和甘氨基酶的突变:对相关疾病的影响
Xiaotong Gu1,2, Aaron S Kovacs1,2, Yoochan Myung1,2
1School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4000, Australia.
Biomolecules
|April 27, 2024
概括
草甘转移酶 (GTs) 和草甘化酶 (GHs) 的致病性突变通常发生在埋藏的蛋白质核和活性位点附近,影响酶功能和蛋白质稳定性. 这项研究确定了治疗开发的关键突变区域.
科学领域:
- 生物化学和分子生物学
- 结构生物学 结构生物学
- 基因组学就是基因组学.
背景情况:
- 甘化是一种常见的翻译后修饰,对蛋白质的功能,稳定性和可溶性至关重要,主要由甘基转移酶 (GTs) 和甘酸化酶 (GHs) 调节.
- GT和GH基因的突变与各种疾病有关,需要更深入地了解它们的结构和功能影响.
- 像ClinVar和UniProt这样的现有数据库为GT和GH提供了有价值的遗传变异数据.
研究的目的:
- 分析GT和GH基因变异的综合数据集,以确定与致病性相关的模式.
- 通过计算和结构生物学方法研究这些变异的结构和功能后果.
- 确定这些酶中易受疾病相关突变的关键区域.
主要方法:
- 从343个GT和GH基因中编译和分析了2603个变异,使用ClinVar和UniProt.数据进行分析.
- 对AlphaFold2预测的蛋白质结构进行了MTR得分分析,以评估变异对二次结构的影响.
- 计算了溶剂可访问性得分和可视化变体,以确定它们在蛋白质结构中的定位.
- 利用mCSM进行变异诱导的蛋白质不稳定性的计算预测.
主要成果:
- 病原性突变经常与贝塔桥次要结构相关.
- 致病变体中的突变残留物显示溶剂可访问性降低,表明它们通常被埋在蛋白质核中.
- 致病变体通常位于酶活性和结合部位附近,可能破坏基质相互作用.
- 计算预测证实,变体可以显著破坏蛋白质结构和功能.
结论:
- 在GT和GH中与疾病相关的突变通常发生在结构关键区域,如埋藏的核心和活跃站点.
- 了解这些突变模式可以了解疾病机制,并有助于识别治疗点.
- 这项研究为开发小分子或生物制剂奠定了基础,以调节酶功能或抵消突变引起的稳定性损失.
相关概念视频
Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
Glucose Transporters
22.7K
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
22.7K
Oligosaccharide Assembly
2.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.8K
Translation
141.9K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
141.9K
Inborn Errors of Metabolism
157
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
157
Protein Glycosylation
6.9K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
6.9K


