S-ribosyl-L-homocysteine (β-form)

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: S-ribosyl-L-homocysteine (β-form)
• 英文别名: S-ribosylhomocysteine；adenine；SRH；(2S)-2-azaniumyl-4-[[(2S,3S,4R,5R)-3,4,5-trihydroxyoxolan-2-yl]methylsulfanyl]butanoate
• 化学式: C₉H₁₇NO₆S
• 分子量: 267.303
• InChiKey: IQFWYNFDWRYSRA-OEQWSMLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  159
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  S-ribosyl-L-homocysteine (β-form) 在 MES buffer 、 E_. coli S-ribosylhomocysteinase 、 5-(2-氨基乙基)二硫代-2-硝基苯甲酸 作用下， 生成 L-高半胱氨酸 、 6-甲基-2-硫代-2,3-二氢-4H-1,3-苯并噁嗪-4-酮
  参考文献：
  名称：

  5-(2-Aminoethyl)dithio-2-nitrobenzoate as a More Base-Stable Alternative to Ellman's Reagent

  摘要：

  (GRAPHICS)5-(2-Aminoethyl)dithio-2-nitrobenzoate (ADNB) reacts with free thiols with kinetics similar to those of Ellman's reagent but has dramatically improved stability under alkaline conditions, making it an excellent alternative to Ellman's reagent for the quantitation of thiol contents and enzymatic assays under basic pH conditions.

  DOI：

  10.1021/ol048404+
• 作为产物：
  描述：

  S-(5'-腺苷)-L-高半胱氨酸 在 5′-methylthioadenosinenucleosidase 、 水 作用下， 生成 S-ribosyl-L-homocysteine (β-form)
  参考文献：
  名称：

  Transition State Structure and Inhibition of Rv0091, a 5′-Deoxyadenosine/5′-methylthioadenosine Nucleosidase from Mycobacterium tuberculosis

  摘要：

  Si-Methylthioadertosine/S-Oenosylhornocxsteine nucleoSidase (MTAN) is a bacterial enzyme that catalyzes the hydrolysis of the N-ribosidic bond- in "S'-inethylthioadenoshie (MTA) and-S-adenosylhom-ocysteitie (SAH). MTAN activity has- be,en: linked to quorum Sensing pathways, polyaMine biosynthesis, and adenine salVage Previously the aiding sequence Of Rv0091 was annotated as a putative (MTA) in Mycobacterium tuberculosis. Rv0091 was expressed 14 Escherithia coli, purified :to -homogeneity., and shown to be a homodimer, consistent with MTANs from other -microorganisms. Substrate specificity for Rv0091 gave a preference for,SCcleoxya,deriosine relative to MTA or SAH. Intrinsic :kinetic isbtope':effects (KIEs) for'.the hydrolysis of [1'-H-3], [1'-C-14] [5-H-3(2)]; and [9-(15)]MTA. were determined to be 1.207, 1.038, 0:998, 1.021, and 0.998, respectively. A model for the transition state structure of Rv0091 'was determined by matching KIE values predicted via quantum cheinical calculations to the'intrinsic KIEs. The transition state shows -a subStantial loss of Cl-,1 N9 bond order,: well -developed oxocarbenium character ofthe ribosyl ring and weak participation of the Water nueleophile. Electrostatic potential surface maps for the Ry0091 transition state structure show, siMilarity to DADMe-irrimucillin yansition state analogues. DADMe-lim-nucillirt transition state analogues showed strong inhibiticin of Rv0091, with:the most potent inhibitor (514iexylthio-DADMe4inmut'illinA): displaying a Ki value of 87 pM.

  DOI：

  10.1021/acschembio.6b00144

文献信息

• Chemical synthesis of S-ribosyl-l-homocysteine and activity assay as a LuxS substrate
  作者：Gang Zhao、Wei Wan、Shahrzad Mansouri、Joshua F Alfaro、Bonnie L Bassler、Kenneth A Cornell、Zhaohui Sunny Zhou

  DOI：10.1016/j.bmcl.2003.09.015

  日期：2003.11

  5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several

  细菌群体感应是由自感应子介导的，细菌是由细菌产生的小信号分子。已经提出，LuxS酶将S-核糖基-L-高半胱氨酸转化为4,5-二羟基-2,3-戊二酮，自动诱导物2（AI-2）的前体。我们在这里报告使用Mitsunobu偶联的S-核糖基-L-高半胱氨酸及其类似物的化学合成。化学合成的核糖基同型半胱氨酸在酶测定法和全细胞群体感应测定法中均已证实是LuxS的底物。还确定了LuxS反应产物的化学实体。已经测试了几种核糖同型半胱氨酸类似物作为LuxS抑制剂。
• Transition State Structure and Inhibition of Rv0091, a 5′-Deoxyadenosine/5′-methylthioadenosine Nucleosidase from <i>Mycobacterium tuberculosis</i>
  作者：Hilda A. Namanja-Magliano、Christopher F. Stratton、Vern L. Schramm

  DOI：10.1021/acschembio.6b00144

  日期：2016.6.17

  Si-Methylthioadertosine/S-Oenosylhornocxsteine nucleoSidase (MTAN) is a bacterial enzyme that catalyzes the hydrolysis of the N-ribosidic bond- in "S'-inethylthioadenoshie (MTA) and-S-adenosylhom-ocysteitie (SAH). MTAN activity has- be,en: linked to quorum Sensing pathways, polyaMine biosynthesis, and adenine salVage Previously the aiding sequence Of Rv0091 was annotated as a putative (MTA) in Mycobacterium tuberculosis. Rv0091 was expressed 14 Escherithia coli, purified :to -homogeneity., and shown to be a homodimer, consistent with MTANs from other -microorganisms. Substrate specificity for Rv0091 gave a preference for,SCcleoxya,deriosine relative to MTA or SAH. Intrinsic :kinetic isbtope':effects (KIEs) for'.the hydrolysis of [1'-H-3], [1'-C-14] [5-H-3(2)]; and [9-(15)]MTA. were determined to be 1.207, 1.038, 0:998, 1.021, and 0.998, respectively. A model for the transition state structure of Rv0091 'was determined by matching KIE values predicted via quantum cheinical calculations to the'intrinsic KIEs. The transition state shows -a subStantial loss of Cl-,1 N9 bond order,: well -developed oxocarbenium character ofthe ribosyl ring and weak participation of the Water nueleophile. Electrostatic potential surface maps for the Ry0091 transition state structure show, siMilarity to DADMe-irrimucillin yansition state analogues. DADMe-lim-nucillirt transition state analogues showed strong inhibiticin of Rv0091, with:the most potent inhibitor (514iexylthio-DADMe4inmut'illinA): displaying a Ki value of 87 pM.
• 5-(2-Aminoethyl)dithio-2-nitrobenzoate as a More Base-Stable Alternative to Ellman's Reagent
  作者：Jinge Zhu、Ilirian Dhimitruka、Dehua Pei

  DOI：10.1021/ol048404+

  日期：2004.10.1

  (GRAPHICS)5-(2-Aminoethyl)dithio-2-nitrobenzoate (ADNB) reacts with free thiols with kinetics similar to those of Ellman's reagent but has dramatically improved stability under alkaline conditions, making it an excellent alternative to Ellman's reagent for the quantitation of thiol contents and enzymatic assays under basic pH conditions.
• Williams–Beuren syndrome‐related methyltransferase WBSCR27: cofactor binding and cleavage
  作者：Sofia S. Mariasina、Chi‐Fon Chang、Olga A. Petrova、Sergey V. Efimov、Vladimir V. Klochkov、Olga I. Kechko、Vladimir A. Mitkevich、Petr V. Sergiev、Olga A. Dontsova、Vladimir I. Polshakov

  DOI：10.1111/febs.15320

  日期：2020.12

  Williams–Beuren syndrome, characterized by numerous physiological and mental problems, is caused by the heterozygous deletion of chromosome region 7q11.23, which results in the disappearance of 26 protein‐coding genes. Protein WBSCR27 is a product of one of these genes whose biological function has not yet been established and for which structural information has been absent until now. Using NMR, we investigated the structural and functional properties of murine WBSCR27. For protein in the apo form and in a complex with S‐(5′‐adenosyl)‐l‐homocysteine (SAH), a complete NMR resonance assignment has been obtained and the secondary structure has been determined. This information allows us to attribute WBSCR27 to Class I methyltransferases. The interaction of WBSCR27 with the cofactor S‐(5′‐adenosyl)‐l‐methionine (SAM) and its metabolic products – SAH, 5′‐deoxy‐5′‐methylthioadenosine (MTA) and 5′‐deoxyadenosine (5′dAdo) – was studied by NMR and isothermal titration calorimetry. SAH binds WBSCR27 much tighter than SAM, leaving open the question of cofactor turnover in the methylation reaction. One possible answer to this question is the presence of weak but detectable nucleosidase activity for WBSCR27. We found that the enzyme catalyses the cleavage of the adenine moiety from SAH, MTA and 5′dAdo, similar to the action of bacterial SAH/MTA nucleosidases. We also found that the binding of SAM or SAH causes a significant change in the structure of WBSCR27 and in the conformational mobility of the protein fragments, which can be attributed to the substrate recognition site. This indicates that the binding of the cofactor modulates the folding of the substrate‐recognizing region of the enzyme.