5,10-methylenetetrahydromethanopterin | 128500-56-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5,10-methylenetetrahydromethanopterin
• 英文别名: methylene-H4MPT；methylenetetrahydromethanopterin；5,10-Methylenetetrahydromethanopterin；(2S)-2-[[(2R,3S,4R,5S)-5-[(2R,3S,4S)-5-[4-[(6S,6aR,7R)-3-amino-6,7-dimethyl-1-oxo-2,5,6,6a,7,9-hexahydroimidazo[1,5-f]pteridin-8-yl]phenyl]-2,3,4-trihydroxypentoxy]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxypentanedioic acid
• CAS: 128500-56-1
• 化学式: C₃₁H₄₅N₆O₁₆P
• 分子量: 788.703
• InChiKey: GBMIGEWJAPFSQI-CAFBYHECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  54
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  336
• 氢给体数：
  11
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  5,10-methylenetetrahydromethanopterin 在 Methanobrevibacter smithii cell extract 作用下， 生成 5,10-methenyltetrahydromethanopterin
  参考文献：
  名称：

  通过稳定同位素标记阐明的产甲烷古细菌中 [Fe]-氢化酶的铁-鸟苷酰吡啶醇辅因子的生物合成

  摘要：

  [Fe]-氢化酶催化从 H(2) 到methenyltetrahydromethanopherin 的可逆氢化物转移，它是产甲烷古细菌中从H(2) 和CO(2) 形成甲烷的中间体。该酶具有独特的活性位点铁-鸟苷基吡啶醇 (FeGP) 辅因子，其中低自旋 Fe(II) 由吡啶醇-N、酰基、两个一氧化碳和酶的半胱氨酸的硫配位。在这里，我们通过将来自标记前体的 (13)C 和 (2)H 掺入到生长产甲烷古菌的辅因子中，并通过随后的 NMR、基质辅助激光解吸/电离时间来研究 FeGP 辅因子的生物合成。飞行质谱（MALDI-TOF-MS），电喷雾电离傅立叶变换离子回旋共振质谱 (ESI-FT-ICR-MS) 和 IR 分析分离的辅因子和参考化合物。发现辅因子的吡啶醇部分由三个乙酸的 C-1、两个乙酸的 C-2、两个丙酮酸的 C-1、一个来自 l-甲硫氨酸的甲基的碳和一个直接来自 CO的碳合成(2)

  DOI：

  10.1021/ja211594m
• 作为产物：
  描述：

  5,10-methenyltetrahydromethanopterin 在 5,10-methenyltetrahydromethanopterin hydrogenase II from Methanocaldococcus jannaschii holo type 、 氢气 作用下， 以 aq. phosphate buffer 为溶剂， 生成 5,10-methylenetetrahydromethanopterin
  参考文献：
  名称：

  Towards a functional identification of catalytically inactive [Fe]‐hydrogenase paralogs

  摘要：

  [Fe]‐hydrogenase (Hmd), an enzyme of the methanogenic energy metabolism, harbors an iron‐guanylylpyridinol (FeGP) cofactor used for H2 cleavage. The generated hydride is transferred to methenyl‐tetrahydromethanopterin (methenyl‐H4MPT+). Most hydrogenotrophic methanogens contain the hmd‐related genes hmdII and hmdIII. Their function is still elusive. We were able to reconstitute the HmdII holoenzyme of Methanocaldococcus jannaschii with recombinantly produced apoenzyme and the FeGP cofactor, which is a prerequisite for in vitro functional analysis. Infrared spectroscopic and X‐ray structural data clearly indicated binding of the FeGP cofactor. Methylene‐H4MPT binding was detectable in the significantly altered infrared spectra of the HmdII holoenzyme and in the HmdII apoenzyme–methylene‐H4MPT complex structure. The related binding mode of the FeGP cofactor and methenyl‐H4MPT+ compared with Hmd and their multiple contacts to the polypeptide highly suggest a biological role in HmdII. However, holo‐HmdII did not catalyze the Hmd reaction, not even in a single turnover process, as demonstrated by kinetic measurements. The found inactivity can be rationalized by an increased contact area between the C‐ and N‐terminal folding units in HmdII compared with in Hmd, which impairs the catalytically necessary open‐to‐close transition, and by an exchange of a crucial histidine to a tyrosine. Mainly based on the presented data, a function of HmdII as Hmd isoenzyme, H2 sensor, FeGP‐cofactor storage protein and scaffold protein for FeGP‐cofactor biosynthesis could be excluded. Inspired by the recently found binding of HmdII to aminoacyl‐tRNA synthetases and tRNA, we tentatively consider HmdII as a regulatory protein for protein synthesis that senses the intracellular methylene‐H4MPT concentration.DatabaseStructural data are available in the Protein Data Bank under the accession numbers 4YT8; 4YT2; 4YT4 and 4YT5.

  DOI：

  10.1111/febs.13351

文献信息

• Dioxygen Sensitivity of [Fe]-Hydrogenase in the Presence of Reducing Substrates
  作者：Gangfeng Huang、Tristan Wagner、Ulrich Ermler、Eckhard Bill、Kenichi Ataka、Seigo Shima

  DOI：10.1002/anie.201712293

  日期：2018.4.23

  the transfer of a hydride ion from H2 to methenyltetrahydromethanopterin (methenyl‐H4MPT+) to form methylene‐H4MPT. Its iron guanylylpyridinol (FeGP) cofactor plays a key role in H2 activation. Evidence is presented for O2 sensitivity of [Fe]‐hydrogenase under turnover conditions in the presence of reducing substrates, methylene‐H4MPT or methenyl‐H4MPT+/H2. Only then, H2O2 is generated, which decomposes

  单铁加氢酶（[Fe]-加氢酶）可逆地催化氢离子从H 2转移至亚甲基四氢甲蝶呤（methenyl-H 4 MPT +），形成亚甲基-H 4 MPT。其胍基铁吡啶铁（FeGP）辅因子在H 2活化中起关键作用。提出了在存在还原性底物，亚甲基-H 4 MPT或亚甲基-H 4 MPT + / H 2的情况下，在周转条件下[Fe]-加氢酶的O 2敏感性的证据。只有这样，H 2 O 2产生，分解FeGP辅因子；如通过光谱分析和失活酶的晶体结构所证明的。O 2还原为H 2 O 2需要还原剂，它可以是[Fe]-加氢酶反应过程中短暂形成的催化中间体。最可能的候选物质是氢化铁。通过催化反应的理论研究已经预测了其存在。该发现支持预测，因为描述了氢化极性化合物的氢化钌配合物的相同类型的还原反应。
• Biosynthesis of the Iron-Guanylylpyridinol Cofactor of [Fe]-Hydrogenase in Methanogenic Archaea as Elucidated by Stable-Isotope Labeling
  作者：Michael Schick、Xiulan Xie、Kenichi Ataka、Jörg Kahnt、Uwe Linne、Seigo Shima

  DOI：10.1021/ja211594m

  日期：2012.2.15

  [Fe]-hydrogenase catalyzes the reversible hydride transfer from H(2) to methenyltetrahydromethanoptherin, which is an intermediate in methane formation from H(2) and CO(2) in methanogenic archaea. The enzyme harbors a unique active site iron-guanylylpyridinol (FeGP) cofactor, in which a low-spin Fe(II) is coordinated by a pyridinol-N, an acyl group, two carbon monoxide, and the sulfur of the enzyme's

  [Fe]-氢化酶催化从 H(2) 到methenyltetrahydromethanopherin 的可逆氢化物转移，它是产甲烷古细菌中从H(2) 和CO(2) 形成甲烷的中间体。该酶具有独特的活性位点铁-鸟苷基吡啶醇 (FeGP) 辅因子，其中低自旋 Fe(II) 由吡啶醇-N、酰基、两个一氧化碳和酶的半胱氨酸的硫配位。在这里，我们通过将来自标记前体的 (13)C 和 (2)H 掺入到生长产甲烷古菌的辅因子中，并通过随后的 NMR、基质辅助激光解吸/电离时间来研究 FeGP 辅因子的生物合成。飞行质谱（MALDI-TOF-MS），电喷雾电离傅立叶变换离子回旋共振质谱 (ESI-FT-ICR-MS) 和 IR 分析分离的辅因子和参考化合物。发现辅因子的吡啶醇部分由三个乙酸的 C-1、两个乙酸的 C-2、两个丙酮酸的 C-1、一个来自 l-甲硫氨酸的甲基的碳和一个直接来自 CO的碳合成(2)
• Towards a functional identification of catalytically inactive [Fe]‐hydrogenase paralogs
  作者：Takashi Fujishiro、Kenichi Ataka、Ulrich Ermler、Seigo Shima

  DOI：10.1111/febs.13351

  日期：2015.9

  [Fe]‐hydrogenase (Hmd), an enzyme of the methanogenic energy metabolism, harbors an iron‐guanylylpyridinol (FeGP) cofactor used for H2 cleavage. The generated hydride is transferred to methenyl‐tetrahydromethanopterin (methenyl‐H4MPT+). Most hydrogenotrophic methanogens contain the hmd‐related genes hmdII and hmdIII. Their function is still elusive. We were able to reconstitute the HmdII holoenzyme of Methanocaldococcus jannaschii with recombinantly produced apoenzyme and the FeGP cofactor, which is a prerequisite for in vitro functional analysis. Infrared spectroscopic and X‐ray structural data clearly indicated binding of the FeGP cofactor. Methylene‐H4MPT binding was detectable in the significantly altered infrared spectra of the HmdII holoenzyme and in the HmdII apoenzyme–methylene‐H4MPT complex structure. The related binding mode of the FeGP cofactor and methenyl‐H4MPT+ compared with Hmd and their multiple contacts to the polypeptide highly suggest a biological role in HmdII. However, holo‐HmdII did not catalyze the Hmd reaction, not even in a single turnover process, as demonstrated by kinetic measurements. The found inactivity can be rationalized by an increased contact area between the C‐ and N‐terminal folding units in HmdII compared with in Hmd, which impairs the catalytically necessary open‐to‐close transition, and by an exchange of a crucial histidine to a tyrosine. Mainly based on the presented data, a function of HmdII as Hmd isoenzyme, H2 sensor, FeGP‐cofactor storage protein and scaffold protein for FeGP‐cofactor biosynthesis could be excluded. Inspired by the recently found binding of HmdII to aminoacyl‐tRNA synthetases and tRNA, we tentatively consider HmdII as a regulatory protein for protein synthesis that senses the intracellular methylene‐H4MPT concentration.DatabaseStructural data are available in the Protein Data Bank under the accession numbers 4YT8; 4YT2; 4YT4 and 4YT5.