IHEP OpenIR  > 多学科研究中心
N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1
Liu, HL; Peng, XH; Zhao, F; Zhang, GB; Tao, Y; Luo, ZF; Li, Y; Teng, MK; Li, X; Wei, SQ; Tao Y(陶冶)
2009
发表期刊BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷号379期号:4页码:1120-1125
通讯作者[Zhao, Fang ; Li, Xu] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Dept Chem Phys, Hefei 230026, Anhui, Peoples R China ; [Peng, Xiaohui ; Luo, Zhaofeng ; Li, Yang ; Teng, Maikun ; Li, Xu] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China ; [Liu, Honglin ; Zhang, Guobin ; Wei, Shiqiang] Univ Sci & Technol China, Natl Synchrotron Radiat Lab, Hefei 230029, Anhui, Peoples R China ; [Peng, Xiaohui ; Li, Yang ; Teng, Maikun ; Li, Xu] Chinese Acad Sci, Key Lab Struct Biol, Anhua 230026, Anhui, Peoples R China ; [Zhao, Fang] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Dept Polymer Sci & Engn, Hefei 230026, Anhui, Peoples R China ; [Tao, Ye] Chinese Acad Sci, Inst High Energy Phys, Beijing 100039, Peoples R China
摘要This study examined recombinant wild-type human phosphoribosylpyrophosphate synthetase 1 (wt-PRS1, EC 2.7.6.1) and the point mutant Asn114Ser PRS1 (N114S-Mutant) in cells of a patient with primary gout. Dynamic light-scattering and sedimentation velocity experiments indicated that the monomeric wt-PRS1 in solution was assembled into hexamers after adding the substrate ATP. However, this ATP-induced aggregation effect was not observed with N114S-Mutant, which has a 50% higher enzymatic activity than that of wt-PRS1. Synchrotron radiation circular dichroism spectroscopy revealed that the point mutation causes an increase of alpha-helix content and a decrease Of turn content. Examination of the crystal structure of wt-PRS1 indicated that 12 hydrogen bonds formed by 6 pairs of N114 and D139 have an important role in stabilizing the hexamer. We suggest that the substitution of S114 for N114 in N114S-Mutant leads to the rupture of 12 hydrogen bonds and breakage of the PO(4)(3-) allosteric site where PO(4)(3-) functions as a fixer of the ATP-binding loop. Therefore, we consider that formation of the hexamer as the structural basis of the ADP allosteric inhibition is greatly weakened by the N114S mutation, and that alteration of the ATP-binding loop conformation is the key factor in the increased activity of N114S-Mutant. These two factors could be responsible for the high level of activity of N114S-Mutant in this patient. (C) 2009 Elsevier Inc. All rights reserved
文章类型Article
关键词Phosphoribosylpyrophosphate synthetase 1 Superactivity ATP Allosteric inhibition Aggregation effect Secondary structure
学科领域Biochemistry & Molecular Biology; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
DOI10.1016/j.bbrc.2009.01.034
URL查看原文
语种英语
WOS类目Biochemistry & Molecular Biology ; Biophysics
WOS记录号WOS:000263336700061
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/239080
专题多学科研究中心
作者单位中国科学院高能物理研究所
推荐引用方式
GB/T 7714
Liu, HL,Peng, XH,Zhao, F,et al. N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2009,379(4):1120-1125.
APA Liu, HL.,Peng, XH.,Zhao, F.,Zhang, GB.,Tao, Y.,...&陶冶.(2009).N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,379(4),1120-1125.
MLA Liu, HL,et al."N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 379.4(2009):1120-1125.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
6183.pdf(485KB)期刊论文作者接受稿开放获取CC BY-NC-SA浏览 请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Liu, HL]的文章
[Peng, XH]的文章
[Zhao, F]的文章
百度学术
百度学术中相似的文章
[Liu, HL]的文章
[Peng, XH]的文章
[Zhao, F]的文章
必应学术
必应学术中相似的文章
[Liu, HL]的文章
[Peng, XH]的文章
[Zhao, F]的文章
相关权益政策
暂无数据
收藏/分享
文件名: 6183.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。