5,6-Dihydroxyindole-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6-Dihydroxyindole-2-carboxylate
• 英文别名: 2-carboxy-5-hydroxy-1H-indol-6-olate
• 化学式: C9H6NO4-
• 分子量: 192.15
• InChiKey: YFTGOBNOJKXZJC-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-Dihydroxyindole-2-carboxylate 、 氧气 生成 水 、 Indole-5,6-quinone-2-carboxylate
  参考文献：
  名称：

  Kobayashi T.; Urabe K.; Winder A., EMBO J, 1994, 0261-4189, 5818-25

  摘要：

  DOI：
• 作为产物：
  描述：

  L-dopachromate 生成 5,6-Dihydroxyindole-2-carboxylate
  参考文献：
  名称：

  新型锌酶多巴色素互变异构酶催化的分子机理。

  摘要：

  多巴色素互变异构酶（DCT; EC 5.3.3.12）在哺乳动物的植物生成生物合成途径中催化L-多巴色素转化为5,6-二羟基吲哚-2-羧酸。该酶也称为TRP2，属于三个金属酶家族，称为酪氨酸酶相关蛋白（TRP）。众所周知，酪氨酸酶在其活性位点具有铜。但是，DCT活性位点中金属离子的性质正在讨论中。尽管基于TRP蛋白质序列之间相似性的理论预测表明存在铜，但是与酪氨酸酶相比，某些金属螯合剂对DCT的抑制模式不同，这表明金属离子的性质可能有所不同。直接估计纯化的DCT制剂中的金属含量表明存在约1。5个锌原子/分子，并且不存在铜。通过用氰化物或邻菲咯啉处理DCT的辅酶制备方法，然后在存在不同离子的条件下进行互变异构酶活性的重建实验，证实DCT活性位点的金属辅因子是锌。我们的结果与在酪氨酸酶经典铜结合位点上与组氨酸同源的高度保守的组氨酸残基与Zn2 +螯合相一致。该发现解释了由DCT催化的反应，即互

  DOI：

  10.1042/bj3130447

文献信息

• Rapid purification and characterization of l-dopachrome-methyl ester tautomerase (macrophage-migration-inhibitory factor) from Trichinella spiralis, Trichuris muris and Brugia pahangi
  作者：Joanne L. PENNOCK、Jerzy M. BEHNKE、Quentin D. BICKLE、Eileen DEVANEY、Richard K. GRENCIS、R. Elwyn ISAAC、George W. P. JOSHUA、Murray E. SELKIRK、Yaobi ZHANG、David J. MEYER

  DOI：10.1042/bj3350495

  日期：1998.11.1

  Macrophage-migration-inhibition factor (MIF) is an essential stimulator of mammalian T-lymphocyte-dependent adaptive immunity, hence MIF orthologues might be expressed by infectious organisms as an immunosubversive stratagem. Since MIF actively catalyses the tautomerization of the methyl ester of l-dopachrome (using dopachrome tautomerase), the occurrence of MIF orthologues in several parasitic helminths was investigated by assaying and characterizing such activity. Evidence of MIF orthologues (dopachrome tautomerase) was found in the soluble fraction of the nematodes Trichinella spiralis (stage 4 larvae) and Trichuris muris (adults), and the filarial nematode Brugia pahangi (adults). The MIF orthologues of Tr. muris(TmMIF) and B. pahangi (BpMIF) were purified to homogeneity using phenyl-agarose chromatography, that of T. spiralis (TsMIF) required a further step: cation-exchange FPLC. Retention time on reverse-phase HPLC and Mr on SDS/PAGE of the nematode MIFs were similar to those of human MIF. N-terminal sequences (19 residues) of TsMIF and TmMIF showed 47 and 36% identity, respectively, with human MIF. The N-terminal sequence of BpMIF (14 residues) was identical to that of an MIF orthologue in the genome of B. malayi (Swiss-Prot, P91850) and showed 43% identity to either human or TsMIF. TsMIF had 10-fold higher dopachrome tautomerase activity than MIF from the other sources. The enzyme activities of TsMIF, BpMIF and TmMIF were less sensitive to inhibition by haematin (I50: > 15 µM, > 15 µM and 2.6 µM, respectively) than that of human MIF (I50 0.2 µM). Significant dopachrome tautomerase or phenyl-agarose-purifiable MIF-like protein was not detected in the soluble fraction of the nematodes Heligmosomoides polygyrus and Nippostrongylus brasiliensis, the cestode Hymenolepis diminuta, or the trematodes Schistosoma mansoni, S. japonicum and S. haematobium, or the free-living nematode, Caenorhabditis elegans, which does contain an MIF-related gene.

  巨噬细胞迁移抑制因子（MIF）是哺乳动物T淋巴细胞依赖性适应性免疫的必要刺激剂，因此MIF同源物可能作为免疫下降策略被感染性生物表达。通过检测和表征这种活性，研究了几种寄生线虫中MIF同源物的存在。在寄生线虫Trichinella spiralis（4期幼虫）和Trichuris muris（成虫），以及丝状线虫Brugia pahangi（成虫）的可溶性分数中发现了MIF同源物（酪氨酸自异构酶）。使用苯基琼脂糖色谱纯化了Tr. muris（TmMIF）和B. pahangi（BpMIF）的MIF同源物，而T. spiralis（TsMIF）则需要进一步步骤：阳离子交换FPLC。线虫MIF在反相HPLC上的保留时间和SDS/PAGE上的Mr与人类MIF类似。TsMIF和TmMIF的N末端序列（19个氨基酸）分别与人类MIF具有47％和36％的同源性。BpMIF（14个氨基酸）的N末端序列与B. malayi基因组中的MIF同源物（Swiss-Prot，P91850）相同，并且与人类或TsMIF的同源性为43％。TsMIF的酪氨酸自异构酶活性比其他来源的MIF高10倍。 TsMIF，BpMIF和TmMIF的酶活性对血红素的抑制不太敏感（I50：> 15 µM，> 15 µM和2.6 µM，分别比人类MIF的I50 0.2 µM低）。在线虫Heligmosomoides polygyrus和Nippostrongylus brasiliensis，绦虫Hymenolepis diminuta或吸虫Schistosoma mansoni，S. japonicum和S. haematobium，或自由生活的线虫Caenorhabditis elegans的可溶性分数中未检测到显着的酪氨酸自异构酶或苯基琼脂糖可纯化的MIF样蛋白。
• Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis
  作者：Timothy H.P. TAN、Steve A.V. EDGERTON、Rashmi KUMARI、Mark S.B. McALISTER、S. Mark ROWE、Sylvia NAGL、Laurence H. PEARL、Murray E. SELKIRK、Albert E. BIANCO、Nicholas F. TOTTY、Chris ENGWERDA、Carolyn A. GRAY、David J. MEYER

  DOI：10.1042/0264-6021:3570373

  日期：2001.7.15

  cDNAs were obtained for macrophage migration-inhibitory factor (MIF)/L-dopachrome methyl ester tautomerase homologues from the parasitic nematodes Trichinella spiralis (TsMIF) and Trichuris trichiura (TtMIF). The translated sequences, which were partly confirmed by sequencing of proteolytic fragments, show 42 and 44%,, identity respectively with human or mouse MIF, and are shorter by one C-terminal residue. Unlike vertebrate MIF and MIF homologues of filarial nematodes, neither TsMIF nor TtMIF contain cysteine residues. Soluble recombinant TsMIF, expressed in Escherichia coli showed secondary structure (by CD spectroscopy) and quaternary structure (by fight-scattering and gel filtration) similar to that of the trimeric mammalian MIFs and D-dopachrome tautomerase. The catalytic specificity of recombinant TsMIF in the ketonization of phenylpyruvate (1.4 x 10(6) M-1 . s(-1)) was comparable with that of human MIF, while that of p-hydroxyphenylpyruvate (9.1 x 10(4) M-1. s(-1)) was 71-fold lower. TsMIF showed high specificity in tautomerization of the methyl ester Of L-dopachrome compared with non-esterified L-dopachrome (> 87000-fold) and a high k(cat). (approximate to4 x 10(4) s(-1)) The crystal structure, determined to 1.65 Angstrom (1 Angstrom = 0.1 nm), was generally similar to that of human MIF, but differed in the boundaries of the putative active-site pocket, which can explain the low activity towards p-hydroxyphenylpyruvate. The central pore was blocked, but was continuous, with the three putative tautomerase sites. Recombinant TsMIF (5 ng/ml-5 pg/ml) inhibited migration of human peripheral-blood mononuclear cells in a man-ner similar to that shown by human MIF, but had no effect from 5 to 500 ng/ml on anti-CD3-stimulated murine T-cell proliferation. TsMIF was detected in supernatants of T. spiralis larvae cultured in vitro at 6 ng/ml (55 ng/mg total secreted protein). In conclusion TsMIF has structural, catalytic and cell-migration-inhibitory properties which indicate that it is partially orthologous to mammalian MIF.
• A Tautomerase-Null Macrophage Migration-Inhibitory Factor (MIF) Gene Knock-In Mouse Model Reveals That Protein Interactions and Not Enzymatic Activity Mediate MIF-Dependent Growth Regulation
  作者：Günter Fingerle-Rowson、Dayananda Rao Kaleswarapu、Corinna Schlander、Nazanin Kabgani、Tania Brocks、Nina Reinart、Raymonde Busch、Anke Schütz、Hongqi Lue、Xin Du、Aihua Liu、Huabao Xiong、Yibang Chen、Alice Nemajerova、Michael Hallek、Jürgen Bernhagen、Lin Leng、Richard Bucala

  DOI：10.1128/mcb.01907-08

  日期：2009.4.1

  Macrophage migration-inhibitory factor (MIF) is an upstream regulator of innate immunity and a potential molecular link between inflammation and cancer. The unusual structural homology between MIF and certain tautomerases, which includes both a conserved substrate-binding pocket and a catalytic N-terminal proline (Pro1), has fueled speculation that an enzymatic reaction underlies MIF's biologic function. To address the functional role of the MIF tautomerase activity in vivo, we created a knock-in mouse in which the endogenous mif gene was replaced by one encoding a tautomerase-null, Pro1 -> Gly1 MIF protein (P1G-MIF). While P1G-MIF is completely inactive catalytically, it maintains significant, albeit reduced, binding to its cell surface receptor (CD74) and to the intracellular binding protein JAB1/CSN5. P1G-MIF knock-in mice (mif(P1G/P1G)) and cells derived from these mice show a phenotype in assays of growth control and tumor induction that is intermediate between those of the wild type (mif(+/+)) and complete MIF deficiency (mif(-/-)). These data provide genetic evidence that MIF's intrinsic tautomerase activity is dispensable for this cytokine's growth-regulatory properties and support a role for the N-terminal region in protein-protein interactions.
• Jimenez-Cervantes C.; Solano F.; Kobayashi T., J Biol Chem, 1994, 0021-9258, 17993-8000
  作者：Jimenez-Cervantes C.、Solano F.、Kobayashi T.、Urabe K.、Hearing V.J.、Lozano J.A.、Garcia-Borron J.C.

  DOI：——

  日期：——