phospho-(S)-4,5-dihydroxy-2,3-pentandione | 1312297-28-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: phospho-(S)-4,5-dihydroxy-2,3-pentandione
• 英文别名: (2S)-2-hydroxy-3,4-diketopentyl phosphate；[(2S)-2-hydroxy-3,4-dioxopentyl] dihydrogen phosphate
• CAS: 1312297-28-1
• 化学式: C₅H₉O₇P
• 分子量: 212.096
• InChiKey: DTZHMTDUIGHESZ-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  phospho-(S)-4,5-dihydroxy-2,3-pentandione 在 luxS regulated G 、 1,4-二巯基-2,3-丁二醇 作用下， 生成 3-hydroxy-2,4-pentadione-5-phosphate 、 3,4,4-trihydroxy-2-pentanone-5-phosphate
  参考文献：
  名称：

  Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

  摘要：

  The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.

  DOI：

  10.1074/jbc.m111.230227
• 作为产物：
  描述：

  1-(2S)-1,4-二氧杂螺[4.5]癸-2-基-1,2-丙二酮 在 luxS regulated kinase 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 以 water-d2 、 水 为溶剂， 反应 0.17h， 生成 phospho-(S)-4,5-dihydroxy-2,3-pentandione
  参考文献：
  名称：

  Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

  摘要：

  The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.

  DOI：

  10.1074/jbc.m111.230227

文献信息

• Crystal Structures of the LsrR Proteins Complexed with Phospho-AI-2 and Two Signal-Interrupting Analogues Reveal Distinct Mechanisms for Ligand Recognition
  作者：Jung-Hye Ha、Yumi Eo、Alexander Grishaev、Min Guo、Jacqueline A. I. Smith、Herman O. Sintim、Eun-Hee Kim、Hae-Kap Cheong、William E. Bentley、Kyoung-Seok Ryu

  DOI：10.1021/ja407068v

  日期：2013.10.16

  Quorum sensing (QS) is a cell-to-cell communication system responsible for a variety of bacterial phenotypes including virulence and biofilm formation. QS is mediated by small molecules, autoinducers (AIs), including AI-2 that is secreted by both Gram-positive and -negative microbes. LsrR is a key transcription regulator that governs the varied downstream processes by perceiving AI-2 signal, but its activation via autoinducer-binding remains poorly understood. Here, we provide detailed regulatory mechanism of LsrR from the crystal structures in complexes with the native signal (phospho-AI-2, D5P) and two quorum quenching antagonists (ribose-5-phosphate, R5P; phospho-isobutyl-AI-2, D8P). Interestingly, the bound D5P and D8P molecules are not the diketone forms but rather hydrated, and the hydrated moiety forms important H-bonds with the carboxylate of D243. The D5P-binding flipped out F124 of the binding pocket, and resulted in the disruption of the dimeric interface-1 by unfolding the alpha 7 segment. However, the same movement of F124 by the D8P'-binding did not cause the unfolding of the alpha 7 segment. Although the LsrR-binding affinity of RSP (K-d, similar to 1 mM) is much lower than that of D5P and D8P (similar to 1.0 and similar to 0.5 mu M), the alpha-anomeric R5P molecule fits into the binding pocket without any structural perturbation, and thus stabilizes the LsrR tetramer. The binding of D5P, not D8P and R5P, disrupted the tetrameric structure and thus is able to activate LsrR. The detailed structural and mechanistic insights from this study could be useful for facilitating design of new antivirulence and antibiofilm agents based on LsrR.
• Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)
  作者：João C. Marques、Pedro Lamosa、Caitlin Russell、Rita Ventura、Christopher Maycock、Martin F. Semmelhack、Stephen T. Miller、Karina B. Xavier

  DOI：10.1074/jbc.m111.230227

  日期：2011.5

  The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.