A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase.
A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase.
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DOI：
10.1371/journal.pone.0184405
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Barton GJ
中科院分区：
文献类型：
--
作者：
Britto-Borges T;Barton GJ
蛋白质O-GlcNAc化（O-GlcNAc）是高等真核生物中一种重要的翻译后修饰（PTM）。O-连接的β-N-乙酰葡糖胺转移酶（OGT）靶向细胞内蛋白质中的特异性丝氨酸和苏氨酸（S/T）。然而，与磷酸化不同的是，已知的O-GlcNAc位点中只有不到25%与明确的序列模式相匹配。因此，O-GlcNAc位点的三维结构的特征在于研究结构在分子识别中的作用。从620个蛋白质中的1，584个O-GlcNAc位点中，143个被定位到通过X射线晶体学确定的蛋白质结构。修饰的S/T在定义蛋白质结构中缺失残基的REM 465字段中注释的可能性高1.7倍，而7个O-GlcNAc位点是溶剂不可及的，不太可能被OGT靶向。具有完整骨架原子的132个位点聚成10个基团，但这些与来自未修饰的S/T的簇难以区分。这表明OGT识别没有普遍的三维基序。将来自620种蛋白质的预测特征与O-GlcNAc酰化蛋白质和球状蛋白质中未修饰的S/T进行比较。Jpred 4预测的二级结构表明，修饰的S/T更可能是卷曲。5/6预测内在紊乱的方法表明O-GlcNAc酰化S/T比未修饰的S/T明显更紊乱。虽然分析没有发现位点三维结构的模式，但它揭示了修饰位点周围的残基可能是无序的，并表明二级结构元件在OGT位点识别中的潜在作用。
Protein O-GlcNAcylation (O-GlcNAc) is an essential post-translational modification (PTM) in higher eukaryotes. The O-linked β-N-acetylglucosamine transferase (OGT), targets specific Serines and Threonines (S/T) in intracellular proteins. However, unlike phosphorylation, fewer than 25% of known O-GlcNAc sites match a clear sequence pattern. Accordingly, the three-dimensional structures of O-GlcNAc sites were characterised to investigate the role of structure in molecular recognition. From 1,584 O-GlcNAc sites in 620 proteins, 143 were mapped to protein structures determined by X-ray crystallography. The modified S/T were 1.7 times more likely to be annotated in the REM465 field which defines missing residues in a protein structure, while 7 O-GlcNAc sites were solvent inaccessible and unlikely to be targeted by OGT. 132 sites with complete backbone atoms clustered into 10 groups, but these were indistinguishable from clusters from unmodified S/T. This suggests there is no prevalent three-dimensional motif for OGT recognition. Predicted features from the 620 proteins were compared to unmodified S/T in O-GlcNAcylated proteins and globular proteins. The Jpred4 predicted secondary structure shows that modified S/T were more likely to be coils. 5/6 methods to predict intrinsic disorder indicated O-GlcNAcylated S/T to be significantly more disordered than unmodified S/T. Although the analysis did not find a pattern in the site three-dimensional structure, it revealed the residues around the modification site are likely to be disordered and suggests a potential role of secondary structure elements in OGT site recognition.
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Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
3.8
作者：
Ma J;Hart GW
通讯作者：
Hart GW
DOI：
10.1073/pnas.152346899
发表时间：
2002-08-06
影响因子：
11.1
作者：
McClain, DA;Lubas, WA;Hanover, JA
通讯作者：
Hanover, JA
影响因子：
14.9
作者：
Drozdetskiy A;Cole C;Procter J;Barton GJ
通讯作者：
Barton GJ
影响因子：
14.9
作者：
Hornbeck PV;Zhang B;Murray B;Kornhauser JM;Latham V;Skrzypek E
通讯作者：
Skrzypek E