PRPP

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: PRPP
• 英文别名: phosphoribosyl pyrophosphate；5-O-phosphono-beta-D-ribofuranosyl diphosphate；[(2S,3R,4S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl] phosphono hydrogen phosphate
• 化学式: C₅H₁₃O₁₄P₃
• 分子量: 390.071
• InChiKey: PQGCEDQWHSBAJP-AIHAYLRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  230
• 氢给体数：
  7
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  烟酰胺 、 PRPP 在 三(3-羟基丙基)膦 、 nicotinamide phosphoribosyltransferase 、 三羟甲基氨基甲烷盐酸盐 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 以 水 为溶剂， 生成 β-烟酰胺单核苷酸
  参考文献：
  名称：

  [EN] DUAL-ACTIVITY NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE INHIBITORS
  [FR] INHIBITEURS DE LA NICOTINAMIDE PHOSPHORIBOSYLTRANSFÉRASE À DOUBLE ACTIVITÉ

  摘要：

  公开号：

  WO2018085379A3

文献信息

• Product Deuterium Isotope Effects for Orotidine 5′-Monophosphate Decarboxylase: Effect of Changing Substrate and Enzyme Structure on the Partitioning of the Vinyl Carbanion Reaction Intermediate
  作者：Krisztina Toth、Tina L. Amyes、Bryant M. Wood、Kui Chan、John A. Gerlt、John P. Richard

  DOI：10.1021/ja102408k

  日期：2010.5.26

  A product deuterium isotope effect (PIE) of 1.0 was determined as the ratio of the yields of [6-(1)H]-uridine 5'-monophosphate (50%) and [6-(2)H]-uridine 5'-monophosphate (50%) from the decarboxylation of orotidine 5'-monophosphate (OMP) in 50/50 (v/v) HOH/DOD catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) from Saccharomyces cerevisiae, Methanothermobacter thermautotrophicus, and Escherichia

  1.0 的产物氘同位素效应 (PIE) 被确定为 [6-(1)H]-尿苷 5'-单磷酸酯 (50%) 和 [6-(2)H]-尿苷 5' 的产率之比-单磷酸盐 (50%) 来自乳清菌素 5'-单磷酸酯 (OMP) 在 50/50 (v/v) HOH/DOD 中由来自酿酒酵母、甲烷嗜热杆菌和嗜热自养菌的乳清酸 5'-单磷酸酯脱羧酶 (OMPDC) 催化大肠杆菌。这种单一的 PIE 消除了酶催化脱羧的建议机制，其中从 Lys-93 到 OMP 的 C-6 的质子转移提供亲电推动，以减少 CO(2) 在协同反应中的损失。我们提出溶剂 H 和 D 的反应完全缺乏选择性，这由 PIE = 1.0 的值暗示，由 Lys-93 侧链的 -CH(2)-NL(3)(+) 基团的受限 CN 键旋转强制执行。0.93 的较小 PIE 被确定为 50/50 (v/v) HOH/DOD 中 OMPDC 催化的 5-氟代乳清酸
• The Conversion of a Phenol to an Aniline Occurs in the Biochemical Formation of the 1-(4-Aminophenyl)-1-deoxy-<scp>d</scp>-ribitol Moiety in Methanopterin
  作者：Robert H. White

  DOI：10.1021/bi200362w

  日期：2011.7.12

  Recent work has demonstrated that 4-hydroxybenzoic acid is the in vivo precursor to the 1-(4-aminophenyl)-1-deoxy-D-ribitol (APDR) moiety present in the C-1 carrier coenzyme methanopterin present in the methanogenic archaea. For this transformation to occur, the hydroxyl group of the 4-hydroxybenzoic acid must be replaced with an amino group at some point in the biosynthetic pathway. Using stable isotopically labeled precursors and liquid chromatography with electrospray-ionization mass spectroscopy, the first step of this transformation in Methanocaldococcus jannaschii occurs by the reaction of 4-hydroxybenzoic acid with phosphoribosyl pyrophosphate (PRPP) to form 4-(beta-D-ribofuranosyl)hydroxybenzene 5'-phosphate (beta-RAH-P). The beta-RAH-P then condenses with L-aspartate in the presence of ATP to form 4-(beta-D-ribofuranosyl)-N-succinylaminobenzene 5'-phosphate (beta-RFSA-P). Elimination of fumarate from beta-RFSA-P produces 4-(beta-D-ribofuranosyl)aminobenzene S'-phosphate (beta-RFA-P), the known precursor to the APDR moiety of methanopterin [White, R. H. (1996) Biochemistry 35, 3447-3456]. This work represents the first biochemical example of the conversion of a phenol to an aniline.
• The Role for Glutamic Acid at Position 196 in Human Hypoxanthine Phosphoribosyltransferase (HPRT) as Investigated Using Site-Directed Mutagenesis
  作者：B. Canyuk、A. E-Wan、W. Keawwijit、T. Nualnoi、L. Sirisatean、P. Tansakul、C. Tanthana

  DOI：10.1080/15257770802146593

  日期：2008.7.23

  The crystal structure of human HPRT reveals the involvement of E196 side chain at the A-B dimer interface. Interference by valine substitution at this position (E196V), as identified in patients with Lesch-Nyhan disease, nearly abolishes enzymatic activity. Kinetic analysis of the active mutants (E196A, E196D, E196Q, and E196R) suggests that interaction between K68 and E196 side chains contributes to stabilization of cis-configuration during the catalytic cycle. The study also provides further insight into the role of A-B dimer interactions relating to K68 in the regulation of cis-trans isomerization that potentially governs the rate-limiting steps in the HPRT reaction.
• Interactions at the 2 and 5 Positions of 5-Phosphoribosyl Pyrophosphate Are Essential in <i>Salmonella typhimurium</i> Quinolinate Phosphoribosyltransferase
  作者：Zainab Bello、Barbara Stitt、Charles Grubmeyer

  DOI：10.1021/bi9018219

  日期：2010.2.23

  Quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) catalyzes an unusual phosphoribosyl transfer that is linked to a decarboxylation reaction to form the NAD precursor nicotinate mononucleotide, carbon dioxide, and pyrophosphate from quinolinic acid (QA) and 5-phosphoribosyl I-pyrophosphate (PRPP). Structural studies and sequence similarities with other PRTases have implicated Glu214, Asp235, Lys153, and Lys284 in contributing to catalysis through direct interaction with PRPP. The four residues were substituted by site-directed mutagenesis. A nadC deletant form of BL21DE3 was created to eliminate trace contamination by chromosomal QAPRTase. The mutant enzymes were readily purified and retained their dimeric aggregation state oil gel filtration. Substitution of Lys153 with Ala resulted in an inactive enzyme, indicating its essential nature. Mutation of Glu214 to Ala or Asp caused at least a 4000-fold reduction in k(cat), with 10-fold increases in K-m and K-D values for PRPP. However, mutation of Glu214 to Gln had only modest effects on ligand binding and catalysis. pH profiles indicated that the deprotonated form of a residue with pK(a) of 6.9 is essential for catalysis, The WT-like pH profile of the E214Q Mutant indicated that Glu214 is not that residue. Mutation of Asp235 to Ala did not affect ligand binding or catalysis. Mutation of Lys284 to Ala decreased k(cat) by 30-fold and increased K-m and K-D values for PRPP by 80-fold and at least 20-fold, respectively. The Study Suggests that Lys153 is necessary for catalysis and important for PRPP binding, Glu214 provides a hydrogen bond necessary for catalysis but does not act as a base or electrostatically to stabilize the transition state, Lys284 is involved in PRPP binding, and Asp235 is not essential.