Structure and Dynamics of N-Glycosylated Human Ribonuclease 1.,Biochemistry

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Structure and Dynamics of N-Glycosylated Human Ribonuclease 1.
Biochemistry ( IF 2.9 ) Pub Date : 2020-06-16 , DOI: 10.1021/acs.biochem.0c00191
Henry R Kilgore ₁ , Andrew P Latham ₁ , Valerie T Ressler ₁ , Bin Zhang ₁ , Ronald T Raines ₁

Affiliation

Glycosylation is a common modification that can endow proteins with altered physical and biological properties. Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88. We have produced the three individual glycoforms that display the core heptasaccharide, Man₅GlcNAc₂, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations. The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that “cap” the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability. In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis. The N-glycosylation of Asn76 has less pronounced consequences. These data highlight the diverse behaviors of Man₅GlcNAc₂ pendants and provide a structural underpinning to the functional consequences of protein glycosylation.

中文翻译：

N-糖基化人核糖核酸酶的结构和动力学1。

糖基化是一种常见的修饰，可以赋予蛋白质改变的物理和生物学特性。核糖核酸酶1（RNase 1）是原型酶RNase A的人类同源物，在天冬酰胺残基34、76和88处经历N联糖基化作用。我们产生了展示核心七糖的三种独立糖型，Man ₅ GlcNAc ₂，并通过小角度X射线散射和分子动力学模拟分析了每种糖型的结构。Asn34上的聚糖相对紧凑且刚性强，提供氢键“封盖”α螺旋C端的羰基，并增强了蛋白质的热稳定性。相反，Asn88上的聚糖具有柔韧性，甚至可以进入酶活性位点，从而阻碍了催化作用。Asn76的N-糖基化作用不太明显。这些数据突出了Man ₅ GlcNAc ₂链坠的不同行为，并提供了蛋白质糖基化功能后果的结构基础。

更新日期：2020-06-16

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