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N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1

文献类型：期刊论文

作者Liu, HL; Peng, XH; Zhao, F; Zhang, GB; Tao, Y; Luo, ZF; Li, Y; Teng, MK; Li, X; Wei, SQ
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
出版日期2009
卷号379期号:4页码:1120-1125
关键词Phosphoribosylpyrophosphate synthetase 1 Superactivity ATP Allosteric inhibition Aggregation effect Secondary structure
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
英文摘要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
学科主题Biochemistry & Molecular Biology; Biophysics
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
原文出处SCI
语种英语
WOS记录号WOS:000263336700061
源URL[http://ir.ihep.ac.cn/handle/311005/239080]  
专题高能物理研究所_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.

入库方式： OAI收割

来源：高能物理研究所

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