细菌病原体中可溶性4-二磷酸胞苷-2-C-甲基-D-赤藓糖醇激酶的表达与特性分析
Expression and characterization of soluble 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from bacterial pathogens.
作者信息
Eoh Hyungjin, Narayanasamy Prabagaran, Brown Amanda C, Parish Tanya, Brennan Patrick J, Crick Dean C
机构信息
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
出版信息
Chem Biol. 2009 Dec 24;16(12):1230-9. doi: 10.1016/j.chembiol.2009.10.014.
Abstract
Many bacterial pathogens utilize the 2-C-methyl-D-erythritol 4-phosphate pathway for biosynthesizing isoprenoid precursors, a pathway that is vital for bacterial survival and absent from human cells, providing a potential source of drug targets. However, the characterization of 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME) kinase (IspE) has been hindered due to a lack of enantiopure CDP-ME and difficulty in obtaining pure IspE. Here, enantiopure CDP-ME was chemically synthesized and recombinant IspE from bacterial pathogens were purified and characterized. Although gene disruption was not possible in Mycobacterium tuberculosis, IspE is essential in Mycobacterium smegmatis. The biochemical and kinetic characteristics of IspE provide the basis for development of a high throughput screen and structural characterization.
摘要
许多细菌病原体利用2-C-甲基-D-赤藓糖醇4-磷酸途径来生物合成类异戊二烯前体，该途径对细菌生存至关重要且在人类细胞中不存在，是潜在的药物靶点来源。然而，由于缺乏对映体纯的4-二磷酸胞苷-2-C-甲基-D-赤藓糖醇（CDP-ME）以及难以获得纯的IspE，4-二磷酸胞苷-2-C-甲基-D-赤藓糖醇激酶（IspE）的特性研究受到了阻碍。在此，通过化学合成获得了对映体纯的CDP-ME，并对来自细菌病原体的重组IspE进行了纯化和特性分析。虽然在结核分枝杆菌中无法进行基因破坏，但IspE在耻垢分枝杆菌中是必需的。IspE的生化和动力学特性为高通量筛选和结构表征的发展提供了基础。
相似文献
1
Expression and characterization of soluble 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from bacterial pathogens.
Chem Biol. 2009 Dec 24;16(12):1230-9. doi: 10.1016/j.chembiol.2009.10.014.
2
Synthesis of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate and kinetic studies of Mycobacterium tuberculosis IspF.
Chem Biol. 2010 Feb 26;17(2):117-22. doi: 10.1016/j.chembiol.2010.01.013.
3
Crystal structure of 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE) from Mycobacterium tuberculosis.
FASEB J. 2011 May;25(5):1577-84. doi: 10.1096/fj.10-175786. Epub 2011 Jan 31.
4
Characterization of Aquifex aeolicus 4-diphosphocytidyl-2C-methyl-d-erythritol kinase - ligand recognition in a template for antimicrobial drug discovery.
FEBS J. 2008 Jun;275(11):2779-94. doi: 10.1111/j.1742-4658.2008.06418.x. Epub 2008 Apr 16.
5
Crystallization and preliminary X-ray analysis of 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE) from Mycobacterium tuberculosis.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Jul 1;67(Pt 7):821-3. doi: 10.1107/S1744309111019567. Epub 2011 Jun 30.
6
Structural modeling identifies Plasmodium vivax 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) as a plausible new antimalarial drug target.
Parasitol Int. 2018 Aug;67(4):375-385. doi: 10.1016/j.parint.2018.03.001. Epub 2018 Mar 14.
7
Crystal structure of IspF from and absence of protein complex assembly amongst IspD/IspE/IspF enzymes in the MEP pathway.
Biosci Rep. 2018 Feb 21;38(1). doi: 10.1042/BSR20171370. Print 2018 Feb 28.
8
Absence of substrate channeling between active sites in the Agrobacterium tumefaciens IspDF and IspE enzymes of the methyl erythritol phosphate pathway.
Biochemistry. 2006 Mar 21;45(11):3548-53. doi: 10.1021/bi0520075.
9
Biosynthesis of isoprenoids: a bifunctional IspDF enzyme from Campylobacter jejuni.
Eur J Biochem. 2004 Jul;271(14):3028-35. doi: 10.1111/j.1432-1033.2004.04234.x.
10
Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development.
J Bacteriol. 2007 Dec;189(24):8922-7. doi: 10.1128/JB.00925-07. Epub 2007 Oct 5.
引用本文的文献
1
Investigating Novel IspE Inhibitors of the MEP Pathway in Mycobacterium.
Microorganisms. 2023 Dec 21;12(1):18. doi: 10.3390/microorganisms12010018.
2
The Multifaceted MEP Pathway: Towards New Therapeutic Perspectives.
Molecules. 2023 Feb 1;28(3):1403. doi: 10.3390/molecules28031403.
3
Comparative Genomic Analysis of Fusobacterium necrophorum Provides Insights into Conserved Virulence Genes.
Microbiol Spectr. 2022 Dec 21;10(6):e0029722. doi: 10.1128/spectrum.00297-22. Epub 2022 Oct 7.
4
New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium.
Front Microbiol. 2016 Sep 13;7:1421. doi: 10.3389/fmicb.2016.01421. eCollection 2016.
5
Metabolic engineering of Bacillus subtilis for terpenoid production.
Appl Microbiol Biotechnol. 2015 Nov;99(22):9395-406. doi: 10.1007/s00253-015-6950-1. Epub 2015 Sep 15.
6
Prolonged-acting, multi-targeting gallium nanoparticles potently inhibit growth of both HIV and mycobacteria in co-infected human macrophages.
Sci Rep. 2015 Mar 6;5:8824. doi: 10.1038/srep08824.
7
Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids.
Microbiol Spectr. 2014;2(4). doi: 10.1128/microbiolspec.MGM2-0021-2013.
8
Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.
FASEB J. 2014 Dec;28(12):5071-82. doi: 10.1096/fj.14-255786. Epub 2014 Aug 13.
9
Synthesis of chirally pure 1-deoxy-d-xylulose-5-phosphate : A substrate for IspC assay to determine inhibitor.
Chem Sci J. 2013 Dec 30;4(2).
10
Mechanistic aspects of carotenoid biosynthesis.
Chem Rev. 2014 Jan 8;114(1):164-93. doi: 10.1021/cr400106y. Epub 2013 Oct 31.
本文引用的文献
1
Chemoenzymatic synthesis of 4-diphosphocytidyl-2-C-methyl-D-erythritol: A substrate for IspE.
Tetrahedron Lett. 2008 Jul 21;49(29-30):4461-4463. doi: 10.1016/j.tetlet.2008.05.074.
2
The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.
Tuberculosis (Edinb). 2009 Jan;89(1):1-11. doi: 10.1016/j.tube.2008.07.004. Epub 2008 Sep 14.
3
Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase.
Bioorg Med Chem Lett. 2008 Oct 1;18(19):5320-3. doi: 10.1016/j.bmcl.2008.08.034. Epub 2008 Aug 14.
4
Dxr is essential in Mycobacterium tuberculosis and fosmidomycin resistance is due to a lack of uptake.
BMC Microbiol. 2008 May 20;8:78. doi: 10.1186/1471-2180-8-78.
5
Characterization of Aquifex aeolicus 4-diphosphocytidyl-2C-methyl-d-erythritol kinase - ligand recognition in a template for antimicrobial drug discovery.
FEBS J. 2008 Jun;275(11):2779-94. doi: 10.1111/j.1742-4658.2008.06418.x. Epub 2008 Apr 16.
6
The structure of Mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery.
BMC Struct Biol. 2007 Oct 23;7:68. doi: 10.1186/1472-6807-7-68.
7
Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development.
J Bacteriol. 2007 Dec;189(24):8922-7. doi: 10.1128/JB.00925-07. Epub 2007 Oct 5.
8
The non-mevalonate pathway of isoprenoid precursor biosynthesis.
J Biol Chem. 2007 Jul 27;282(30):21573-7. doi: 10.1074/jbc.R700005200. Epub 2007 Apr 18.
9
Production of isoprenoid pharmaceuticals by engineered microbes.
Nat Chem Biol. 2006 Dec;2(12):674-81. doi: 10.1038/nchembio836.
10
Category B potential bioterrorism agents: bacteria, viruses, toxins, and foodborne and waterborne pathogens.
Infect Dis Clin North Am. 2006 Jun;20(2):395-421, x. doi: 10.1016/j.idc.2006.02.002.
Zotero 插件