乙酰羟酸合成酶结构研究
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- 英文论文题名：Structural Research of Acetohydroxyacid Synthase
- 论文作者：张营营 ; 李欣 ; 牛聪伟 ; 席真
- 英文论文作者：Yingying.Zhang ; X.Li ; C.Niu ; Z.Xi ; State Key Laboratory of Elemento-Organic Chemistry ; University of Nankai ; State Key Laboratory of Medicinal Chemical Biology ; University of Nankai
- 年：2016
- 作者机构：南开大学化学学院元素有机化学国家重点实验室;南开大学生命科学学院药物化学生物学国家重点实验室;
- 论文关键词：支链氨基酸 ; 乙酰羟基酸合成酶 ; 晶体结构
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：O629.8;TQ450.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：223k
- 原文格式：D
- 会议级别：全国
摘要
乙酰乳酸合成酶是非常重要的超高效绿色除草剂的靶标,是支链氨基酸生物合成途径中的第一个关键酶,由催化亚基和调控亚基组成。迄今为止,我们对AHAS的催化反应机制、调控亚基对催化亚基的激活机制以及支链氨基酸对全酶活性的反馈调控机制都还知之甚少。近年来,单独的催化亚基或者调控亚基不断被解析,但是目前为止,AHAS全酶复合物的晶体结构及其与缬氨酸的复合物晶体结构还没有报道,这严重阻碍了新型AHAS抑制剂的设计,因此全酶复合物的解析对于探究AHAS的化学生物学调控及其作用机制至关重要。于是,我们在实验室之前的工作的基础上,进一步对大肠杆菌蛋白序列结构进行分析,构建了相应的蛋白突变体。目前初步得到了全酶复合物的晶体,并正在对其进行解析。
Acetohydroxyacid synthase is a very important target of ultra-efficient green herbicides,which catalyzes the first common step in the biosynthesis of branched chain amino acids and composed by catalytic subunit(CSU) and regulatory subunit(RSU).So far the mechanisms of catalysis,activation and feedback inhibition for AHAS were poorly understood,so the study on the structure of AHAS is very important to explain these mechanisms.In recent years the crystal structures of AHAS catalytic and regulatory subunits have been determined by X-ray diffraction,respectively.However,the crystal structure of the holoenzyme has not been reported yet.AHAS sequences and structures from various species were analysed,mutants of AHAS protein were developed in order to increase the stabilization of protein and to aid the structure solution.In addition,we did structural biology study on E.coli AHAS holoenzyme complex.The crystals of E.coli AHAS holoenzyme complex and preliminary analysis were completed.
Acetohydroxyacid synthase is a very important target of ultra-efficient green herbicides,which catalyzes the first common step in the biosynthesis of branched chain amino acids and composed by catalytic subunit(CSU) and regulatory subunit(RSU).So far the mechanisms of catalysis,activation and feedback inhibition for AHAS were poorly understood,so the study on the structure of AHAS is very important to explain these mechanisms.In recent years the crystal structures of AHAS catalytic and regulatory subunits have been determined by X-ray diffraction,respectively.However,the crystal structure of the holoenzyme has not been reported yet.AHAS sequences and structures from various species were analysed,mutants of AHAS protein were developed in order to increase the stabilization of protein and to aid the structure solution.In addition,we did structural biology study on E.coli AHAS holoenzyme complex.The crystals of E.coli AHAS holoenzyme complex and preliminary analysis were completed.
引文
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[6]Silvaggi N.R.;Martin L.J.;Schwalbe H.Journal of the American Chemical Society,2007,129(22):7114-7120..
[7]Pang S.S.;.Duggleby R.G.;Guddat L.W.Journal of Molecular Biology,2002,317(2):249-262.6.
[2]Zhao,Y.;Niu,C.;Wen,X.et al.ChemBioChem,2013,14(6):746-752.
[3]Silvaggi N.R.;Martin L.J.;Schwalbe H.Journal of the American Chemical Society,2007,129(22):7114-7120.
[4]Mccour,TJA.;Pang,S.S,;King-scott,J.et al.Proc Natl Acad Sci USA,2006,103(3):569-573.
[5]Gedi,V;Yoon,MY.FEBS Journal,2012,279:946-963
[6]Silvaggi N.R.;Martin L.J.;Schwalbe H.Journal of the American Chemical Society,2007,129(22):7114-7120..
[7]Pang S.S.;.Duggleby R.G.;Guddat L.W.Journal of Molecular Biology,2002,317(2):249-262.6.