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保留糖基转移酶甘露糖甘油酸合酶的催化机制。

The Catalytic Mechanism of the Retaining Glycosyltransferase Mannosylglycerate Synthase.

机构信息

LAQV@REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007, Porto, Portugal.

出版信息

Chemistry. 2021 Oct 7;27(56):13998-14006. doi: 10.1002/chem.202101724. Epub 2021 Sep 8.

DOI:10.1002/chem.202101724
PMID:34355437
Abstract

To protect their intracellular proteins, extremophile microorganisms synthesize molecules called compatible solutes. These molecules are the result of the attachment of a small negatively charged molecule to a sugar molecule. It has been found that these molecules, not only protect the microorganism against osmotic stress but also against other extreme conditions. They can also confer protection against extreme conditions to isolated enzymes from different organisms making them an exciting prospect for potential biotechnological applications. One of the most widespread compatible solute in hyperthermophile organisms is the molecule 2-O-α-D-mannosyl-D-glycerate (MG). In addition to confer protection to proteins against extreme conditions, MG was found to prevent Alzheimer's β-amyloid aggregation and reduce α-synuclein fibril formation in Parkinson's disease. In this work we studied, using computational methods, the catalytic mechanism of the synthesis of MG by the enzyme mannosylglycerate synthase (MGS) from the thermophilic bacteria Rhodothermus marinus.

摘要

为了保护其细胞内蛋白质,极端微生物合成了称为相容性溶质的分子。这些分子是将一个小带负电荷的分子附着到糖分子上的结果。已经发现,这些分子不仅可以保护微生物免受渗透胁迫,还可以免受其他极端条件的影响。它们还可以赋予来自不同生物体的分离酶对抗极端条件的保护,这使得它们成为潜在生物技术应用的令人兴奋的前景。在高温微生物中最广泛的相容溶质之一是 2-O-α-D-甘露糖基-D-甘油酸(MG)分子。除了保护蛋白质免受极端条件的影响外,MG 还被发现可以阻止阿尔茨海默氏症β-淀粉样蛋白聚集,并减少帕金森氏病中α-突触核蛋白纤维的形成。在这项工作中,我们使用计算方法研究了来自嗜热细菌 Rhodothermus marinus 的甘露糖甘油酸合酶(MGS)合成 MG 的催化机制。

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The Catalytic Mechanism of the Retaining Glycosyltransferase Mannosylglycerate Synthase.保留糖基转移酶甘露糖甘油酸合酶的催化机制。
Chemistry. 2021 Oct 7;27(56):13998-14006. doi: 10.1002/chem.202101724. Epub 2021 Sep 8.
2
Biosynthesis of mannosylglycerate in the thermophilic bacterium Rhodothermus marinus. Biochemical and genetic characterization of a mannosylglycerate synthase.嗜热细菌海栖热袍菌中甘露糖基甘油酸的生物合成。甘露糖基甘油酸合酶的生化及遗传学特性
J Biol Chem. 1999 Dec 10;274(50):35407-14. doi: 10.1074/jbc.274.50.35407.
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Structural dissection and high-throughput screening of mannosylglycerate synthase.甘露糖基甘油酸合酶的结构剖析与高通量筛选
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Substrate and metal ion promiscuity in mannosylglycerate synthase.甘露糖甘油酸合酶的底物和金属离子混杂性。
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Compatible Solutes in the Thermophilic Bacteria Rhodothermus marinus and "Thermus thermophilus".嗜热菌 Rhodothermus marinus 和“Thermus thermophilus”中的相容溶质。
Appl Environ Microbiol. 1995 Jun;61(6):2351-7. doi: 10.1128/aem.61.6.2351-2357.1995.
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A gene from the mesophilic bacterium Dehalococcoides ethenogenes encodes a novel mannosylglycerate synthase.来自嗜温细菌脱卤球菌的一个基因编码一种新型甘露糖基甘油酸合酶。
J Bacteriol. 2004 Jul;186(13):4075-84. doi: 10.1128/JB.186.13.4075-4084.2004.
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Combined effect of the growth temperature and salinity of the medium on the accumulation of compatible solutes by Rhodothermus marinus and Rhodothermus obamensis.培养基的生长温度和盐度对海栖热袍菌和奥巴马热袍菌相容性溶质积累的联合效应。
Extremophiles. 1999 May;3(2):163-72. doi: 10.1007/s007920050112.
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Structural analysis of Thermus thermophilus HB27 mannosyl-3-phosphoglycerate synthase provides evidence for a second catalytic metal ion and new insight into the retaining mechanism of glycosyltransferases.嗜热栖热菌 HB27 甘露糖基-3-磷酸甘油酸合酶的结构分析为第二个催化金属离子提供了证据,并深入了解了糖基转移酶的保留机制。
J Biol Chem. 2010 Jun 4;285(23):17857-68. doi: 10.1074/jbc.M109.095976. Epub 2010 Mar 31.
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Specialized roles of the two pathways for the synthesis of mannosylglycerate in osmoadaptation and thermoadaptation of Rhodothermus marinus.两条甘露糖基甘油酸合成途径在海栖热袍菌渗透适应和热适应中的特殊作用。
J Biol Chem. 2004 Mar 12;279(11):9892-8. doi: 10.1074/jbc.M312186200. Epub 2003 Dec 29.
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Synthesis of GDP-mannose and mannosylglycerate from labeled mannose by genetically engineered Escherichia coli without loss of specific isotopic enrichment.通过基因工程改造的大肠杆菌从标记的甘露糖合成GDP-甘露糖和甘露糖甘油酸,且不损失特定的同位素富集。
Appl Environ Microbiol. 2003 Jan;69(1):233-40. doi: 10.1128/AEM.69.1.233-240.2003.

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