Structural Changes Induced by the Deamidation and Isomerization of Asparagine Revealed by the Crystal Structure of Ustilago sphaerogena Ribonuclease U2B
Structural Changes Induced by the Deamidation and Isomerization of Asparagine Revealed by the Crystal Structure of Ustilago sphaerogena Ribonuclease U2B
复制标题
DOI：
10.1002/bip.21514
复制
发表时间：
2010-11-01
期刊：
影响因子：
2.9
通讯作者：
Noguchi, Shuji
中科院分区：
文献类型：
--
作者：
Noguchi, Shuji
在生理条件下，天冬酰胺通过琥珀酰亚胺非酶促脱酰胺和异构化为异天冬氨酸（isoAsp）。虽然大量的蛋白质已被报道含有异天冬氨酸，有关的三维结构的蛋白质含有异天冬氨酸的信息仍然有限。我们已经结晶了含有球形黑粉菌核糖核酸酶U2 B的isoAsp，并在1.32埃分辨率下测定了晶体结构。结构表明，isoAsp 32的形成诱导α-螺旋从Asp 29到Asp 34的单转解折叠，并且从Asp 29到Arg 35的区域形成U形环结构。电子密度图显示isoAsp 32在C-α原子处保留L-构型。IsoAsp 32在C-α-C-β键附近呈扭曲构象，多肽链在isoAsp 32处弯曲约90度。IsoAsp 32从蛋白质表面突出，主链中的异常β-肽键和侧链中的α-羧酸酯完全暴露。该结构表明蛋白质中Asn的脱酰胺和isoAsp的形成可赋予免疫原性。(C)2010 Wiley Periodicals，Inc. Biopolymers 93：1003-1010，2010.
Under physiological conditions, the deamidation and isomerization of asparagine to isoaspartate (isoAsp) proceeds nonenzymatically via succinimide. Although a large number of proteins have been reported to contain isoAsp, information concerning the three-dimensional structure of proteins containing isoaspartate is still limited. We have crystallized isoAsp containing Ustilago sphaerogena ribonuclease U2B, and determined the crystal structure at 1.32 angstrom resolution. The structure revealed that the formation of isoAsp32 induces a single turn unfolding of the alpha-helix from Asp29 to Asp34, and the region from Asp29 to Arg35 forms a U-shaped loop structure. The electron density map shows that isoAsp32 retained the L-configuration at the C-alpha atom. IsoAsp32 is in gauche conformation about a C-alpha-C-beta bond, and the polypeptide chain bends by similar to 90 degrees at isoAsp32. IsoAsp32 protrudes from the surface of the protein, and the abnormal beta-peptide bond in the main-chain and alpha-carboxylate in the side-chain is fully exposed. The structure suggests that the deamidation of the Asn and the isoAsp formation in proteins could confer immunogenicity. (C) 2010 Wiley Periodicals, Inc. Biopolymers 93: 1003-1010, 2010.