评估NAD(H)类似物作为克氏锥虫S-腺苷同型半胱氨酸水解酶的选择性抑制剂。
Evaluation of NAD(H) analogues as selective inhibitors for Trypanosoma cruzi S-adenosylhomocysteine hydrolase.
作者信息
Li Qing-Shan, Cai Sumin, Fang Jianwen, Borchardt Ronald T, Kuczera Krzysztof, Middaugh C Russell, Schowen Richard L
机构信息
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas, USA.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):473-84. doi: 10.1080/15257770903044572.
Abstract
S-Adenosylhomocysteine (AdoHcy) hydrolases (SAHHs) from human sources (Hs-SAHHs) bind the cofactor NAD(+) more tightly than several parasitic SAHHs by around 1000-fold. This property suggests the cofactor binding site of this essential enzyme as a potential anti-parasitic drug target, e.g., against SAHH from Trypansoma cruzi (Tc-SAHH). The on-rate and off-rate constants and the equilibrium dissociation constants were determined for NAD(+)/NADH analogues and suggested that NADH analogues were the most promising for selective inhibition of Tc-SAHH. None significantly inhibited Hs-SAHH while S-NADH and H-NADH (see Figure 1) reduced the catalytic activity of Tc-SAHH to < 10% in six minutes of exposure.
摘要
来自人类的S-腺苷同型半胱氨酸（AdoHcy）水解酶（Hs-SAHHs）与辅因子NAD(+)的结合比几种寄生虫SAHHs紧密约1000倍。这一特性表明这种必需酶的辅因子结合位点是一个潜在的抗寄生虫药物靶点，例如针对克氏锥虫的SAHH（Tc-SAHH）。测定了NAD(+)/NADH类似物的结合速率常数、解离速率常数和平衡解离常数，结果表明NADH类似物对选择性抑制Tc-SAHH最有前景。没有一种能显著抑制Hs-SAHH，而S-NADH和H-NADH（见图1）在暴露6分钟内将Tc-SAHH的催化活性降低至<10%。
相似文献
1
Evaluation of NAD(H) analogues as selective inhibitors for Trypanosoma cruzi S-adenosylhomocysteine hydrolase.评估NAD(H)类似物作为克氏锥虫S-腺苷同型半胱氨酸水解酶的选择性抑制剂。
Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):473-84. doi: 10.1080/15257770903044572.
2
The rationale for targeting the NAD/NADH cofactor binding site of parasitic S-adenosyl-L-homocysteine hydrolase for the design of anti-parasitic drugs.将寄生性S-腺苷-L-高半胱氨酸水解酶的NAD/NADH辅因子结合位点作为抗寄生虫药物设计靶点的基本原理。
Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):485-503. doi: 10.1080/15257770903051031.
3
Comparative kinetics of cofactor association and dissociation for the human and trypanosomal S-adenosylhomocysteine hydrolases. 1. Basic features of the association and dissociation processes.人源和锥虫源S-腺苷同型半胱氨酸水解酶辅因子结合与解离的比较动力学。1. 结合和解离过程的基本特征。
Biochemistry. 2007 May 15;46(19):5798-809. doi: 10.1021/bi700170m. Epub 2007 Apr 21.
4
Comparative kinetics of cofactor association and dissociation for the human and trypanosomal S-adenosylhomocysteine hydrolases. 2. The role of helix 18 stability.人源和锥虫源S-腺苷同型半胱氨酸水解酶辅因子结合与解离的比较动力学。2. 螺旋18稳定性的作用。
Biochemistry. 2008 Apr 29;47(17):4983-91. doi: 10.1021/bi800175g. Epub 2008 Apr 8.
5
The antiviral drug ribavirin is a selective inhibitor of S-adenosyl-L-homocysteine hydrolase from Trypanosoma cruzi.抗病毒药物利巴韦林是克氏锥虫S-腺苷-L-高半胱氨酸水解酶的选择性抑制剂。
Bioorg Med Chem. 2007 Dec 1;15(23):7281-7. doi: 10.1016/j.bmc.2007.08.029. Epub 2007 Aug 24.
6
Comparative kinetics of cofactor association and dissociation for the human and trypanosomal S-adenosylhomocysteine hydrolases. 3. Role of lysyl and tyrosyl residues of the C-terminal extension.人源和锥虫 S-腺苷同型半胱氨酸水解酶的辅因子结合和解离的比较动力学。3. C 末端延伸的赖氨酸和酪氨酸残基的作用。
Biochemistry. 2010 Sep 28;49(38):8434-41. doi: 10.1021/bi1007595.
7
Copper ions inhibit S-adenosylhomocysteine hydrolase by causing dissociation of NAD+ cofactor.铜离子通过导致烟酰胺腺嘌呤二核苷酸（NAD+）辅因子解离来抑制S-腺苷同型半胱氨酸水解酶。
Biochemistry. 2007 Oct 16;46(41):11451-8. doi: 10.1021/bi700395d. Epub 2007 Sep 25.
8
Trypanothione Reductase: A Target for the Development of Anti- Trypanosoma cruzi Drugs.锥虫硫醇还原酶：开发抗克氏锥虫药物的靶点
Mini Rev Med Chem. 2017;17(11):939-946. doi: 10.2174/1389557517666170315145410.
9
Trypanosoma cruzi: molecular cloning and characterization of the S-adenosylhomocysteine hydrolase.克氏锥虫：S-腺苷同型半胱氨酸水解酶的分子克隆与特性分析
Exp Parasitol. 2003 Oct;105(2):149-58. doi: 10.1016/j.exppara.2003.10.001.
10
Rational design of nitrofuran derivatives: Synthesis and valuation as inhibitors of Trypanosoma cruzi trypanothione reductase.硝基呋喃衍生物的合理设计：作为克氏锥虫锥虫硫醇还原酶抑制剂的合成与评估
Eur J Med Chem. 2017 Jan 5;125:1088-1097. doi: 10.1016/j.ejmech.2016.10.055. Epub 2016 Oct 24.
引用本文的文献
1
Methyltransferases: Functions and Applications.甲基转移酶：功能与应用。
Chembiochem. 2022 Sep 16;23(18):e202200212. doi: 10.1002/cbic.202200212. Epub 2022 Jul 5.
2
-Adenosyl-L-Homocysteine Hydrolase Inhibition by a Synthetic Nicotinamide Cofactor Biomimetic.一种合成烟酰胺辅因子仿生剂对腺苷-L-高半胱氨酸水解酶的抑制作用
Front Microbiol. 2018 Mar 21;9:505. doi: 10.3389/fmicb.2018.00505. eCollection 2018.
3
A genomic scale map of genetic diversity in Trypanosoma cruzi.克氏锥虫遗传多样性的基因组规模图谱。
BMC Genomics. 2012 Dec 27;13:736. doi: 10.1186/1471-2164-13-736.
本文引用的文献
1
Comparative kinetics of cofactor association and dissociation for the human and trypanosomal S-adenosylhomocysteine hydrolases. 2. The role of helix 18 stability.人源和锥虫源S-腺苷同型半胱氨酸水解酶辅因子结合与解离的比较动力学。2. 螺旋18稳定性的作用。
Biochemistry. 2008 Apr 29;47(17):4983-91. doi: 10.1021/bi800175g. Epub 2008 Apr 8.
2
Comparative kinetics of cofactor association and dissociation for the human and trypanosomal S-adenosylhomocysteine hydrolases. 1. Basic features of the association and dissociation processes.人源和锥虫源S-腺苷同型半胱氨酸水解酶辅因子结合与解离的比较动力学。1. 结合和解离过程的基本特征。
Biochemistry. 2007 May 15;46(19):5798-809. doi: 10.1021/bi700170m. Epub 2007 Apr 21.
3
Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human malaria parasite Plasmodium falciparum.来自人类疟原虫恶性疟原虫的S-腺苷-L-高半胱氨酸水解酶的晶体结构。
J Mol Biol. 2004 Oct 29;343(4):1007-17. doi: 10.1016/j.jmb.2004.08.104.
4
Trypanosoma cruzi: molecular cloning and characterization of the S-adenosylhomocysteine hydrolase.克氏锥虫：S-腺苷同型半胱氨酸水解酶的分子克隆与特性分析
Exp Parasitol. 2003 Oct;105(2):149-58. doi: 10.1016/j.exppara.2003.10.001.
5
Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor.NAD⁺和NADH的差异结合使转录共抑制因子羧基末端结合蛋白能够作为一种代谢传感器。
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9202-7. doi: 10.1073/pnas.1633591100. Epub 2003 Jul 18.
6
Catalytic strategy of S-adenosyl-L-homocysteine hydrolase: transition-state stabilization and the avoidance of abortive reactions.S-腺苷-L-高半胱氨酸水解酶的催化策略：过渡态稳定及避免无效反应
Biochemistry. 2003 Feb 25;42(7):1900-9. doi: 10.1021/bi0262350.
7
Inhibition of S-adenosylhomocysteine hydrolase by acyclic sugar adenosine analogue D-eritadenine. Crystal structure of S-adenosylhomocysteine hydrolase complexed with D-eritadenine.无环糖腺苷类似物D-香菇嘌呤对S-腺苷同型半胱氨酸水解酶的抑制作用。与D-香菇嘌呤复合的S-腺苷同型半胱氨酸水解酶的晶体结构。
J Biol Chem. 2002 Mar 1;277(9):7477-82. doi: 10.1074/jbc.M109187200. Epub 2001 Dec 10.
8
Computational characterization of substrate binding and catalysis in S-adenosylhomocysteine hydrolase.S-腺苷同型半胱氨酸水解酶中底物结合与催化作用的计算表征
Biochemistry. 2001 Dec 18;40(50):15143-52. doi: 10.1021/bi015690d.
9
Structure and function of S-adenosylhomocysteine hydrolase.S-腺苷高半胱氨酸水解酶的结构与功能
Cell Biochem Biophys. 2000;33(2):101-25. doi: 10.1385/CBB:33:2:101.
10
Overexpression, purification, and characterization of S-adenosylhomocysteine hydrolase from Leishmania donovani.来自杜氏利什曼原虫的S-腺苷同型半胱氨酸水解酶的过表达、纯化及特性分析
Arch Biochem Biophys. 2000 Nov 15;383(2):272-80. doi: 10.1006/abbi.2000.2087.
Zotero 插件