5-methyl-D-thioribose | 91297-36-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-methyl-D-thioribose
• 英文别名: 5-methylthioribose；S-methyl-D-5-thio-ribose；S-methyl-ξ-D-5-thio-ribofuranose；5-methylthio-D-ribose；(3R,4S,5S)-5-(methylsulfanylmethyl)oxolane-2,3,4-triol
• CAS: 91297-36-8
• 化学式: C₆H₁₂O₄S
• 分子量: 180.225
• InChiKey: OLVVOVIFTBSBBH-JDJSBBGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  95.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-methyl-D-thioribose 在 吡啶 、 叠氮化四丁基铵 作用下， 以 乙腈 为溶剂， 反应 21.0h， 生成 O²,O³-diacetyl-1-(2,6-diazido-purin-9-yl)-S-methyl-β-D-5-thio-1-deoxy-ribofuranose
  参考文献：
  名称：

  涉及腺嘌呤的反应的连续荧光测定

  摘要：

  5'-甲硫腺苷磷酸化酶（MTAP）和5'-甲硫腺苷核苷酶（MTAN）分别催化5'-甲硫腺苷（MTA）的磷酸解和水解。两种酶的底物KM值都很低。这些酶的动力学测定具有挑战性，因为反应物 MTA 和产物腺嘌呤的紫外吸收光谱相似。我们报告了一种使用 2-氨基-5'-甲硫腺苷 (2AMTA) 作为 MTAP 和 MTAN 酶的替代底物的新测定方法。 2AMTA 水解或磷酸解形成 2,6-二氨基嘌呤，这是一种荧光且易于定量的产物。我们用人类 MTAP、细菌 MTAN 来动力学表征 2AMTA，并使用 2,6-二氨基嘌呤作为酵母腺嘌呤磷酸核糖基转移酶的荧光底物。使用 2AMTA 作为底物，对 MTAP 和 MTAN 的三过渡态类似物抑制剂的解离常数进行动力学表征。通过 MTA 连续荧光测定获得的动力学值与之前测量的文献值非常一致，但实验误差较小。从核糖和 2,6-二氯嘌呤进行化学合成，得到草酸盐形式的结晶

  DOI：

  10.1021/acs.analchem.6b03621
• 作为产物：
  描述：

  甲基-2,3-O-异亚丙基-beta-D-呋喃核糖苷 在 吡啶 、 盐酸 、 甲基磺酰氯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 5-methyl-D-thioribose
  参考文献：
  名称：

  涉及腺嘌呤的反应的连续荧光测定

  摘要：

  5'-甲硫腺苷磷酸化酶（MTAP）和5'-甲硫腺苷核苷酶（MTAN）分别催化5'-甲硫腺苷（MTA）的磷酸解和水解。两种酶的底物KM值都很低。这些酶的动力学测定具有挑战性，因为反应物 MTA 和产物腺嘌呤的紫外吸收光谱相似。我们报告了一种使用 2-氨基-5'-甲硫腺苷 (2AMTA) 作为 MTAP 和 MTAN 酶的替代底物的新测定方法。 2AMTA 水解或磷酸解形成 2,6-二氨基嘌呤，这是一种荧光且易于定量的产物。我们用人类 MTAP、细菌 MTAN 来动力学表征 2AMTA，并使用 2,6-二氨基嘌呤作为酵母腺嘌呤磷酸核糖基转移酶的荧光底物。使用 2AMTA 作为底物，对 MTAP 和 MTAN 的三过渡态类似物抑制剂的解离常数进行动力学表征。通过 MTA 连续荧光测定获得的动力学值与之前测量的文献值非常一致，但实验误差较小。从核糖和 2,6-二氯嘌呤进行化学合成，得到草酸盐形式的结晶

  DOI：

  10.1021/acs.analchem.6b03621

文献信息

• Crystal Structure of <i>Aeromonas hydrophila</i> Cytoplasmic 5′-Methylthioadenosine/<i>S</i>-Adenosylhomocysteine Nucleosidase
  作者：Jinli Chen、Wei Liu、Lulu Wang、Fei Shang、Yuanyuan Chen、Jing Lan、Peng Gao、Nam-Chul Ha、Chunshan Quan、Ki Hyun Nam、Yongbin Xu

  DOI：10.1021/acs.biochem.9b00174

  日期：2019.7.23

  5′-Methylthioadenosine/S-adenosyl-l-homocysteine (MTA/SAH) nucleosidase (MTAN) is an important enzyme in a number of critical biological processes. Mammals do not express MtaN, making this enzyme an attractive antibacterial drug target. In pathogen Aeromonas hydrophila, two MtnN subfamily genes (MtaN-1 and MtaN-2) play important roles in the periplasm and cytosol, respectively. We previously reported structural and functional analyses of MtaN-1, but little is known regarding MtaN-2 due to the lack of a crystal structure. Here, we determined the crystal structure of cytosolic A. hydrophila MtaN-2 in complex with adenine (ADE), which is a cleavage product of adenosine. AhMtaN-1 and AhMtaN-2 exhibit a high degree of similarity in the α–β–α sandwich fold of the core structural motif. However, there is a structural difference in the nonconserved extended loop between β7 and α3 that is associated with the channel depth of the substrate-binding pocket and dimerization. The ADE molecules in the substrate-binding pockets of AhMtaN-1 and AhMtaN-2 are stabilized with π–π stacking by Trp199 and Phe152, respectively, and the hydrophobic residues surrounding the ribose-binding sites differ. A structural comparison of AhMtaN-2 with other MtaN proteins showed that MtnN subfamily proteins exhibit a unique substrate-binding surface and dimerization interface.

  5′-甲硫基腺苷/S-腺苷-l-高半胱氨酸（MTA/SAH）核苷酸酶（MTAN）是许多关键生物过程中的重要酶。哺乳动物不表达 MtaN，因此该酶是一个极具吸引力的抗菌药物靶点。在病原体嗜水气单胞菌（Aeromonas hydrophila）中，两个 MtnN 亚家族基因（MtaN-1 和 MtaN-2）分别在周质和细胞质中发挥重要作用。我们以前曾报道过 MtaN-1 的结构和功能分析，但由于缺乏晶体结构，人们对 MtaN-2 知之甚少。在这里，我们测定了细胞质嗜水杆菌 MtaN-2 与腺嘌呤（ADE）（腺嘌呤是腺苷的裂解产物）复合物的晶体结构。AhMtaN-1和AhMtaN-2在核心结构基团的α-β-α三明治折叠中表现出高度的相似性。然而，β7 和 α3 在非保留延伸环上存在结构差异，这与底物结合口袋的通道深度和二聚化有关。AhMtaN-1和AhMtaN-2底物结合口袋中的ADE分子分别通过Trp199和Phe152的π-π堆积而稳定，核糖结合位点周围的疏水残基也有所不同。AhMtaN-2与其他MtaN蛋白的结构比较表明，MtnN亚家族蛋白表现出独特的底物结合表面和二聚化界面。
• Characterization of 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidases from Borrelia burgdorferi: Antibiotic targets for Lyme disease
  作者：Kenneth A. Cornell、Reece J. Knippel、Gerald R. Cortright、Meghan Fonken、Christian Guerrero、Amy R. Hall、Kristen A. Mitchell、John H. Thurston、Patrick Erstad、Aoxiang Tao、Dong Xu、Nikhat Parveen

  DOI：10.1016/j.bbagen.2019.129455

  日期：2020.1

  that specific activity rapidly dropped as the length of the 5′-alkylthio substitution increased. Non-hydrolysable nucleoside transition state analogs demonstrated sub-nanomolar enzyme inhibition constants. Lastly, two late stage transition state analogs exerted in vitro IC50 values of 0.3–0.4 μg/mL against cultured B. burgdorferi cells. Conclusion B. burgdorferi is unusual in that it expresses three distinct

  背景 伯氏疏螺旋体引起莱姆病，这是美国最常见的壁虱传播疾病。疾病控制与预防中心估计，在美国，莱姆病的发病率现在每年达到300,000例。早期的勃氏疏螺旋体感染通常可以通过口服抗生素治疗，但是晚期疾病更难以治疗，更可能导致治疗后的莱姆病综合症。 方法 在这里，我们研究了三种独特的5'-甲基硫代腺苷/ S-腺苷同型半胱氨酸（MTA / SAH）核苷酶（MTN或MTAN，EC 3.2.2.9），它们在伯氏疏螺旋体中拯救了腺嘌呤和蛋氨酸，并探讨了它们作为治疗莱姆病的抗生素靶标的潜力疾病。重组疏螺旋体中期票据中表达并从纯化的大肠杆菌（E.coli） 。使用紫外分光光度法对酶的活性，特异性和抑制作用进行了广泛表征。使用生物发光的BacTiter-Glo™分析评估了MTN抑制剂的体外抗生素活性。 结果 三种Borrelia MTN对天然底物MTA，SAH和5'-脱氧腺苷均表现出独特的活性。对底物类似物的
• Structural and Functional Analyses of Periplasmic 5′-Methylthioadenosine/<i>S</i>-Adenosylhomocysteine Nucleosidase from <i>Aeromonas hydrophila</i>
  作者：Yongbin Xu、Lulu Wang、Jinli Chen、Jing Zhao、Shengdi Fan、Yuesheng Dong、Nam-Chul Ha、Chunshan Quan

  DOI：10.1021/acs.biochem.7b00691

  日期：2017.10.10

  The Gram-negative, rod-shaped bacterium Aeromonas hydrophila has two multifunctional 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) enzymes, MtaN-1 and MtaN-2, that differ from those in other bacteria. These proteins are essential for several metabolic pathways, including biological methylation, polyamine biosynthesis, methionine recycling, and bacterial quorum sensing. To gain insight into how these two proteins function, we determined four high-resolution crystal structures of MtaN-1 in its apo form and in complex with the substrates S-adenosyl-l-homocysteine, 5′-methylthioadenosine, and 5′-deoxyadenosine. We found that the domain structures were generally similar, although slight differences were evident. The crystal structure demonstrates that AhMtaN-1 has an extension of the binding pocket and revealed that a tryptophan in the active site (Trp199) may play a major role in substrate binding, unlike in other MTAN proteins. Mutation of the Trp199 residue completely abolished the enzyme activity. Trp199 was identified as an active site residue that is essential for catalysis. Furthermore, biochemical characterization of AhMtaN-1 and AhMtaN-2 demonstrated that AhMtaN-1 exhibits inherent trypsin resistance that is higher than that of AhMtaN-2. Additionally, the thermally unfolded AhMtaN-2 protein is capable of refolding into active forms, whereas the thermally unfolded AhMtaN-1 protein does not have this ability. Examining the different biochemical characteristics related to the functional roles of AhMtaN-1 and AhMtaN-2 would be interesting. Indeed, the biochemical characterization of these structural features would provide a structural basis for the design of new antibiotics against A. hydrophila.

  革兰氏阴性杆状细菌嗜水气单胞菌有两种多功能5′-甲基硫代腺苷/S-腺苷高半胱氨酸核苷酸酶（MTAN）酶，即MtaN-1和MtaN-2，它们与其他细菌中的酶不同。这些蛋白对于多种代谢途径至关重要，包括生物甲基化、多胺生物合成、蛋氨酸循环和细菌群体感应。为了深入了解这两种蛋白的功能，我们确定了MtaN-1四种高分辨率晶体结构，包括无配体形式以及与底物S-腺苷-L-高半胱氨酸、5′-甲基硫代腺苷和5′-脱氧腺苷的复合物。我们发现，虽然存在明显差异，但结构域结构总体相似。晶体结构表明，AhMtaN-1具有延伸的结合口袋，并揭示了活性位点中的色氨酸（Trp199）可能在底物结合中发挥重要作用，这一点与其他MTAN蛋白不同。Trp199残基的突变完全消除了酶活性。Trp199被确定为催化所需的活性位点残基。此外，AhMtaN-1和AhMtaN-2的生化特性表明，AhMtaN-1具有比AhMtaN-2更高的固有抗胰蛋白酶性。此外，热解折叠的AhMtaN
• <i>Escherichia coli</i> <i>S</i>-adenosylhomocysteine/5′-methylthioadenosine nucleosidase. Purification, substrate specificity and mechanism of action
  作者：F Della Ragione、M Porcelli、M Cartenì-Farina、V Zappia、A E Pegg

  DOI：10.1042/bj2320335

  日期：1985.12.1

  S-Adenosylhomocysteine/5′-methylthioadenosine nucleosidase (EC 3.2.2.9) was purified to homogeneity from Escherichia coli to a final specific activity of 373 mumol of 5′-methylthioadenosine cleaved/min per mg of protein. Affinity chromatography on S-formycinylhomocysteine-Sepharose is the key step of the purification procedure. The enzyme, responsible for the cleavage of the glycosidic bond of both S-adenosylhomocysteine and 5′-methylthioadenosine, was partially characterized. The apparent Km for 5′-methylthioadenosine is 0.4 microM, and that for S-adenosylhomocysteine is 4.3 microM. The maximal rate of cleavage of S-adenosylhomocysteine is approx. 40% of that of 5′-methylthioadenosine. Some 25 analogues of the two naturally occurring thioethers were studied as potential substrates or inhibitors of the enzyme. Except for the analogues modified in the 5′-position of the ribose moiety or the 2-position of the purine ring, none of the compounds tested was effective as a substrate. Moreover, 5′-methylthioformycin, 5′-chloroformycin, S-formycinylhomocysteine, 5′-methylthiotubercidin and S-tubercidinylhomocysteine were powerful inhibitors of the enzyme activity. The results obtained allow the hypothesis of a mechanism of enzymic catalysis requiring as a key step the protonation of N-7 of the purine ring.

  S-腺苷基同型半胱氨酸/5'-甲硫氨酸核苷酸酶（EC 3.2.2.9）已从大肠杆菌中纯化至同质性，最终比活性为每毫克蛋白质分解373微摩尔5'-甲硫氨酸/分钟。S-甲基替福辛-硒酸聚糖凝胶亲和层析是纯化过程的关键步骤。该酶负责水解S-腺苷基同型半胱氨酸和5'-甲硫氨酸的糖苷键，并进行部分表征。5'-甲硫氨酸的表观Km为0.4微米，S-腺苷基同型半胱氨酸的表观Km为4.3微米。S-腺苷基同型半胱氨酸的最大分解速率约为5'-甲硫氨酸的40％。研究了25种两种天然硫醚的类似物作为酶的潜在底物或抑制剂。除了核糖基的5'-位置或嘌呤环的2-位置被修饰的类似物以外，测试的化合物都不是有效的底物。此外，5'-甲硫替福辛、5'-氯替福辛、S-甲基替福辛-硒酸、5'-甲硫嘌呤核苷、S-嘌呤核苷-硒酸均是酶活性的强力抑制剂。所得结果允许假设酶催化机制的关键步骤需要嘌呤环N-7的质子化。
• Plant 5-Methylthioribose Kinase
  作者：Andrzej Guranowski

  DOI：10.1104/pp.71.4.932

  日期：1983.4.1

  ions tested, only Mg(2+) and Mn(2+) acted as cofactors. The curve of kinase initial velocity versus pH reaches plateau at pH 10 to 10.5. The K(m) values calculated for 5-methylthioribose and ATP are 4.3 and 8.3 micromolar, respectively.Among nucleoside triphosphates tested as potential phosphate donors, only dATP could substitute in the reaction for ATP. 5-Isobutylthioribose, an analog of 5-methylthioribose

  5-甲基硫代核糖激酶（一种催化 1-磷酸-5-甲基硫代核糖的 ATP 依赖性形成的酶）的活性已在各种高等植物物种的提取物中得到揭示。从黄羽扇豆 (Lupinus luteus L. cv Topaz) 种子提取物中获得了近 2,000 倍的纯化酶。根据凝胶过滤判断，天然酶的分子量为 70,000。羽扇豆 5-甲基硫代核糖激酶对二价金属离子有严格的要求。在测试的离子中，只有 Mg(2+) 和 Mn(2+) 充当辅助因子。激酶初始速度对 pH 的曲线在 pH 10 到 10.5 时达到平台。为 5-甲基硫代核糖和 ATP 计算的 K(m) 值分别为 4.3 和 8.3 微摩尔。在作为潜在磷酸盐供体测试的三磷酸核苷中，只有 dATP 可以替代 ATP 的反应。5-异丁基硫代核糖（5-甲基硫代核糖的类似物）也被证明是γ-ATP-磷酸受体。该化合物可抑制 1-phospho-5-methylthioribose