• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

白三烯 C4 合酶的两种精氨酸残基的催化结构。

The catalytic architecture of leukotriene C4 synthase with two arginine residues.

机构信息

Structural Biophysics Laboratory, RIKEN SPring-8 Center, Harima Institute, Sayo, Hyogo, Japan.

出版信息

J Biol Chem. 2011 May 6;286(18):16392-401. doi: 10.1074/jbc.M110.150177. Epub 2011 Mar 16.

DOI:10.1074/jbc.M110.150177
PMID:21454538
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3091245/
Abstract

Leukotriene (LT) C(4) and its metabolites, LTD(4) and LTE(4), are involved in the pathobiology of bronchial asthma. LTC(4) synthase is the nuclear membrane-embedded enzyme responsible for LTC(4) biosynthesis, catalyzing the conjugation of two substrates that have considerably different water solubility; that amphipathic LTA(4) as a derivative of arachidonic acid and a water-soluble glutathione (GSH). A previous crystal structure revealed important details of GSH binding and implied a GSH activating function for Arg-104. In addition, Arg-31 was also proposed to participate in the catalysis based on the putative LTA(4) binding model. In this study enzymatic assay with mutant enzymes demonstrates that Arg-104 is required for the binding and activation of GSH and that Arg-31 is needed for catalysis probably by activating the epoxide group of LTA(4).

摘要

白三烯 (LT) C(4) 及其代谢物 LTD(4) 和 LTE(4) 参与支气管哮喘的病理生物学。LTC(4) 合酶是负责 LTC(4) 生物合成的核膜嵌入酶，催化两个具有明显不同水溶性的底物的结合；即作为花生四烯酸衍生物的亲脂性 LTA(4)和水溶性谷胱甘肽 (GSH)。先前的晶体结构揭示了 GSH 结合的重要细节，并暗示 Arg-104 具有 GSH 激活功能。此外，基于假定的 LTA(4)结合模型，还提出 Arg-31 参与催化。在这项研究中，用突变酶进行的酶促分析表明，Arg-104 对于 GSH 的结合和激活是必需的，而 Arg-31 可能通过激活 LTA(4)的环氧化物基团来参与催化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/443041181b04/zbc0241161880005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/e326e1093b9c/zbc0241161880001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/66ed1035eb47/zbc0241161880002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/f0d176b8183b/zbc0241161880003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/bc3c67ebf9c6/zbc0241161880004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/443041181b04/zbc0241161880005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/e326e1093b9c/zbc0241161880001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/66ed1035eb47/zbc0241161880002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/f0d176b8183b/zbc0241161880003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/bc3c67ebf9c6/zbc0241161880004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/3091245/443041181b04/zbc0241161880005.jpg

相似文献

1
The catalytic architecture of leukotriene C4 synthase with two arginine residues.白三烯 C4 合酶的两种精氨酸残基的催化结构。
J Biol Chem. 2011 May 6;286(18):16392-401. doi: 10.1074/jbc.M110.150177. Epub 2011 Mar 16.
2
Arginine 104 is a key catalytic residue in leukotriene C4 synthase.精氨酸 104 是白三烯 C4 合酶的关键催化残基。
J Biol Chem. 2010 Dec 24;285(52):40771-6. doi: 10.1074/jbc.M110.105940. Epub 2010 Oct 27.
3
Pre-steady-state kinetic characterization of thiolate anion formation in human leukotriene C₄ synthase.人白三烯 C₄ 合酶中硫醇阴离子形成的预稳态动力学特征。
Biochemistry. 2012 Jan 31;51(4):848-56. doi: 10.1021/bi201402s. Epub 2012 Jan 23.
4
Leukotriene C(4) synthase.白三烯C4合成酶
Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):111-6. doi: 10.1016/s0952-3278(03)00071-1.
5
The enhanced affinity for thiolate anion and activation of enzyme-bound glutathione is governed by an arginine residue of human Mu class glutathione S-transferases.人 Mu 类谷胱甘肽 S-转移酶的一个精氨酸残基决定了对硫醇阴离子的增强亲和力以及酶结合型谷胱甘肽的活化。
J Biol Chem. 2000 Feb 4;275(5):3296-304. doi: 10.1074/jbc.275.5.3296.
6
Crystal structures of leukotriene C4 synthase in complex with product analogs: implications for the enzyme mechanism.白三烯 C4 合酶与产物类似物复合物的晶体结构：对酶机制的启示。
J Biol Chem. 2014 Feb 21;289(8):5199-207. doi: 10.1074/jbc.M113.534628. Epub 2013 Dec 23.
7
Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase.人白三烯C4合酶合成炎症介质的结构基础。
Nature. 2007 Aug 2;448(7153):613-6. doi: 10.1038/nature06009. Epub 2007 Jul 15.
8
A positively charged amino acid proximal to the C-terminus of TM17 of MRP1 is indispensable for GSH-dependent binding of substrates and for transport of LTC4.多药耐药相关蛋白1（MRP1）的跨膜区17（TM17）C末端附近的一个带正电荷的氨基酸对于谷胱甘肽（GSH）依赖的底物结合以及白三烯C4（LTC4）的转运是不可或缺的。
Biochemistry. 2002 Dec 3;41(48):14132-40. doi: 10.1021/bi026443s.
9
Catalytic characterization of human microsomal glutathione S-transferase 2: identification of rate-limiting steps.人微粒体谷胱甘肽 S-转移酶 2 的催化特性：限速步骤的鉴定。
Biochemistry. 2013 Mar 12;52(10):1755-64. doi: 10.1021/bi3014104. Epub 2013 Feb 27.
10
Formation of murine macrophage-derived 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid (FOG7) is catalyzed by leukotriene C4 synthase.小鼠巨噬细胞衍生的5-氧代-7-谷胱甘肽基-8,11,14-二十碳三烯酸（FOG7）的形成由白三烯C4合酶催化。
J Biol Chem. 2002 Mar 1;277(9):7037-43. doi: 10.1074/jbc.M108942200. Epub 2001 Dec 17.

引用本文的文献

1
Structure Bioinformatics of Six Human Integral Transmembrane Enzymes and their AlphaFold3 Predicted Water-Soluble QTY Analogs: Insights into FACE1 and STEA4 Binding Mechanisms.六种人类整合膜酶及其AlphaFold3预测的水溶性QTY类似物的结构生物信息学：对FACE1和STEA4结合机制的见解
Pharm Res. 2025 Feb;42(2):291-305. doi: 10.1007/s11095-025-03822-6. Epub 2025 Feb 18.
2
Development and Validation of Methodologies for the Identification of Specialized Pro-Resolving Lipid Mediators and Classic Eicosanoids in Biological Matrices.生物基质中特异性促消退脂质介质和经典类花生酸鉴定方法的开发与验证
J Am Soc Mass Spectrom. 2024 Oct 2;35(10):2331-2343. doi: 10.1021/jasms.4c00211. Epub 2024 Sep 9.
3

本文引用的文献

1
A tale of two acids: when arginine is a more appropriate acid than H3O+.两种酸的故事：当精氨酸比 H3O+更合适作为酸时。
J Phys Chem B. 2010 Jul 15;114(27):8994-9001. doi: 10.1021/jp100961s.
2
Leukotriene E4-induced pulmonary inflammation is mediated by the P2Y12 receptor.白三烯E4诱导的肺部炎症由P2Y12受体介导。
J Exp Med. 2009 Oct 26;206(11):2543-55. doi: 10.1084/jem.20091240. Epub 2009 Oct 12.
3
Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells.树突状细胞通过识别屋尘螨中的Dectin-2触发半胱氨酰白三烯的生成。
The enzymology of human eicosanoid pathways: the lipoxygenase branches.
人类二十烷酸途径的酶学：脂氧合酶分支。
Mol Biol Rep. 2020 Sep;47(9):7189-7207. doi: 10.1007/s11033-020-05698-8. Epub 2020 Aug 3.
4
Leukotriene biosynthetic enzymes as therapeutic targets.白三烯生物合成酶作为治疗靶点。
J Clin Invest. 2018 Jul 2;128(7):2680-2690. doi: 10.1172/JCI97945.
5
Leukotriene receptors as potential therapeutic targets.白三烯受体作为潜在的治疗靶点。
J Clin Invest. 2018 Jul 2;128(7):2691-2701. doi: 10.1172/JCI97946. Epub 2018 May 14.
6
Regulation of inflammation by lipid mediators in oral diseases.脂质介质在口腔疾病中对炎症的调节作用。
Oral Dis. 2017 Jul;23(5):576-597. doi: 10.1111/odi.12544. Epub 2016 Aug 4.
7
A dynamic Asp-Arg interaction is essential for catalysis in microsomal prostaglandin E2 synthase.动态的天冬氨酸-精氨酸相互作用对于微粒体前列腺素E2合酶的催化作用至关重要。
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):972-7. doi: 10.1073/pnas.1522891113. Epub 2016 Jan 11.
8
Structure and inhibition of mouse leukotriene C4 synthase.小鼠白三烯C4合成酶的结构与抑制作用
PLoS One. 2014 May 8;9(5):e96763. doi: 10.1371/journal.pone.0096763. eCollection 2014.
9
Crystal structures of leukotriene C4 synthase in complex with product analogs: implications for the enzyme mechanism.白三烯 C4 合酶与产物类似物复合物的晶体结构：对酶机制的启示。
J Biol Chem. 2014 Feb 21;289(8):5199-207. doi: 10.1074/jbc.M113.534628. Epub 2013 Dec 23.
10
Humidity control and hydrophilic glue coating applied to mounted protein crystals improves X-ray diffraction experiments.应用于固定蛋白质晶体的湿度控制和亲水胶涂层可改善X射线衍射实验。
Acta Crystallogr D Biol Crystallogr. 2013 Sep;69(Pt 9):1839-49. doi: 10.1107/S0907444913018027. Epub 2013 Aug 17.
J Immunol. 2009 Jan 15;182(2):1119-28. doi: 10.4049/jimmunol.182.2.1119.
4
Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors.在缺乏半胱氨酰白三烯1和2受体的小鼠中，对白三烯E4具有优先选择性的一种独特受体的功能识别
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16695-700. doi: 10.1073/pnas.0808993105. Epub 2008 Oct 17.
5
Leukotriene E4 activates peroxisome proliferator-activated receptor gamma and induces prostaglandin D2 generation by human mast cells.白三烯E4激活过氧化物酶体增殖物激活受体γ并诱导人肥大细胞产生前列腺素D2。
J Biol Chem. 2008 Jun 13;283(24):16477-87. doi: 10.1074/jbc.M705822200. Epub 2008 Apr 14.
6
Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis.参与半胱氨酰白三烯生物合成的一种人类膜蛋白的晶体结构。
Nature. 2007 Aug 2;448(7153):609-12. doi: 10.1038/nature05936. Epub 2007 Jul 15.
7
Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase.人白三烯C4合酶合成炎症介质的结构基础。
Nature. 2007 Aug 2;448(7153):613-6. doi: 10.1038/nature06009. Epub 2007 Jul 15.
8
Density-functional study of mechanisms for the cofactor-free decarboxylation performed by uroporphyrinogen III decarboxylase.尿卟啉原III脱羧酶催化的无辅因子脱羧反应机制的密度泛函研究
J Phys Chem B. 2005 Sep 29;109(38):18195-200. doi: 10.1021/jp051792s.
9
RIKEN structural genomics beamlines at the SPring-8; high throughput protein crystallography with automated beamline operation.日本理化学研究所（RIKEN）在SPring-8的结构基因组学光束线；通过自动光束线操作实现高通量蛋白质晶体学。
J Struct Funct Genomics. 2006 Mar;7(1):15-22. doi: 10.1007/s10969-005-9005-5. Epub 2006 Apr 28.
10
Cysteinyl leukotrienes regulate Th2 cell-dependent pulmonary inflammation.半胱氨酰白三烯调节Th2细胞依赖性肺部炎症。
J Immunol. 2006 Apr 1;176(7):4440-8. doi: 10.4049/jimmunol.176.7.4440.