3-hydroxyanthranilate | 1074-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-hydroxyanthranilate
• 英文别名: 2-Amino-3-hydroxybenzoate；2-amino-3-carboxyphenolate
• CAS: 1074-80-2
• 化学式: C₇H₆NO₃
• 分子量: 152.13
• InChiKey: WJXSWCUQABXPFS-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-hydroxyanthranilate 在 3-hydroxyanthranilate 3,4-dioxygenase N₂₇A mutant 、 氧气 作用下， 以 aq. buffer 为溶剂， 生成 (2Z)-2-氨基-3-[(1Z)-3-氧代-1-丙烯-1-基]-2-丁烯二酸
  参考文献：
  名称：

  Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities

  摘要：

  3-Hydroxyanthranilate 3,4-dioxygenase (HAO) is an iron-dependent protein that activates O-2 and inserts both oxygen atoms into 3-hydroxyanthranilate (3-HAA). An intriguing question is how HAO can rapidly bind O-2, even though local O-2 concentrations and diffusion rates are relatively low. Here, a close inspection of the HAO structures revealed that substrate- and inhibitor-bound structures exhibit a closed conformation with three hydrophobic loop regions moving toward the catalytic iron center, whereas the ligand-free structure is open. We hypothesized that these loop movements enhance O-2 binding to the binary complex of HAO and 3-HAA. We found that the carboxyl end of 3-HAA triggers changes in two loop regions and that the third loop movement appears to be driven by an H-bond interaction between Asn(27) and Ile(142). Mutational analyses revealed that N27A, I142A, and I142P variants cannot form a closed conformation, and steady-state kinetic assays indicated that these variants have a substantially higher K-m for O-2 than WT HAO. This observation suggested enhanced hydrophobicity at the iron center resulting from the concerted loop movements after the binding of the primary substrate, which is hydrophilic. Given that O-2 is nonpolar, the increased hydrophobicity at the iron center of the binary complex appears to be essential for rapid O-2 binding and activation, explaining the reason for the 3-HAA-induced loop movements. Because substrate binding-induced open-to-closed conformational changes are common, the results reported here may help further our understanding of how oxygen is enriched in nonheme iron-dependent dioxygenases.

  DOI：

  10.1074/jbc.ra118.002698
• 作为产物：
  描述：

  3-羟基-L-犬尿氨酸 、 水 生成 3-hydroxyanthranilate 、 氢(+1)阳离子 、 L-丙氨酸
  参考文献：
  名称：

  Crystal Structure of Homo sapiens Kynureninase^,

  摘要：

  Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.

  DOI：

  10.1021/bi0616697

文献信息

• Structural Studies on 3-Hydroxyanthranilate-3,4-dioxygenase:  The Catalytic Mechanism of a Complex Oxidation Involved in NAD Biosynthesis^,
  作者：Yang Zhang、Keri L. Colabroy、Tadhg P. Begley、Steven E. Ealick

  DOI：10.1021/bi047353l

  日期：2005.5.1

  tryptophan to quinolinate, the universal de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide. The enzyme requires Fe2+ as a cofactor and is inactivated by 4-chloro-3-hydroxyanthranilate. HAD from Ralstonia metallidurans was crystallized, and the structure was determined at 1.9 A resolution. The structures of HAD complexed with the inhibitor 4-chloro-3-hydroxyanthranilic acid and either

  3-羟基邻氨基苯甲酸酯-3,4-二加氧酶（HAD）催化从色氨酸到喹啉酸酯（烟酰胺腺嘌呤二核苷酸吡啶环的通用前体）的生物合成途径的最终酶促步骤中3-羟基邻氨基苯甲酸的氧化环打开。该酶需要Fe2 +作为辅助因子，并被4-氯-3-羟基邻氨基苯甲酸灭活。使来自Ralstonia metallidurans的HAD结晶，并以1.9 A的分辨率确定其结构。与抑制剂4-氯-3-羟基邻氨基苯甲酸和分子氧或一氧化氮络合的HAD的结构在2.0 A分辨率下测定，与3-羟基邻氨基苯甲酸酯络合物的HAD的结构在3.2 A分辨率下测定。HAD是具有亚单位拓扑的同型二聚体，具有亚铜桶折叠的特征。每个单体包含两个铁结合位点。催化铁被His51，Glu57和His95用作配体，被深埋在β桶内。另一个铁位点形成一个靠近溶剂表面的FeS4中心，其中硫原子由Cys125，Cys128，Cys162和Cys165提供。两个铁位点之
• Characterization of the anthranilate degradation pathway in Geobacillus thermodenitrificans NG80-2
  作者：Xueqian Liu、Yangpeng Dong、Xiaomin Li、Yi Ren、Yanxia Li、Wei Wang、Lei Wang、Lu Feng

  DOI：10.1099/mic.0.031880-0

  日期：2010.2.1

  Anthranilate is an important intermediate of tryptophan metabolism. In this study, a hydroxylase system consisting of an FADH₂-utilizing monooxygenase (GTNG_3160) and an FAD reductase (GTNG_3158), as well as a bifunctional riboflavin kinase/FMN adenylyltransferase (GTNG_3159), encoded in the anthranilate degradation gene cluster inGeobacillus thermodenitrificansNG80-2 were functionally characterizedin vitro. GTNG_3159 produces FAD to be reduced by GTNG_3158 and the reduced FAD (FADH₂) is utilized by GTNG_3160 to convert anthranilate to 3-hydroxyanthranilate (3-HAA), which is further degraded to acetyl-CoA through ameta-cleavage pathway also encoded in the gene cluster. Utilization of this pathway for the degradation of anthranilate and tryptophan by NG80-2 under physiological conditions was confirmed by real-time RT-PCR analysis of representative genes. This is believed to be the first time that the degradation pathway of anthranilate via 3-HAA has been characterized in a bacterium. This pathway is likely to play an important role in the survival ofG. thermodenitrificansin the oil reservoir conditions from which strain NG80-2 was isolated.

  Anthranilate是色氨酸代谢的重要中间体。在这项研究中，位于Geobacillus thermodenitrificans NG80-2的anthranilate降解基因簇中编码的一个由FAD还原酶（GTNG_3158）和一个FADH2利用单加氧酶（GTNG_3160）组成的羟化酶系统，以及一个双功能核黄素激酶/FMN腺苷酰转移酶（GTNG_3159）在体外进行了功能特性描述。GTNG_3159产生FAD，被GTNG_3158还原，而还原的FAD（FADH2）被GTNG_3160利用，将anthranilate转化为3-羟基anthranilate（3-HAA），后者通过基因簇中编码的meta-断裂途径进一步降解为乙酰辅酶A。通过代表性基因的实时RT-PCR分析，证实了NG80-2在生理条件下利用此途径降解anthranilate和色氨酸。这被认为是第一次在细菌中表征了通过3-HAA的anthranilate降解途径。这条途径很可能在NG80-2分离的油藏条件下发挥重要作用，有助于其生存。
• Fawaz F.; Jones G.H., J Biol Chem, 1988, 0021-9258, 4602-6
  作者：Fawaz F.、Jones G.H.

  DOI：——

  日期：——
• Crystal structure of 3-hydroxyanthranilic acid 3,4-dioxygenase from Saccharomyces cerevisiae: A special subgroup of the type III extradiol dioxygenases
  作者：X. Li

  DOI：10.1110/ps.051967906

  日期：——

  Abstract3‐Hydroxyanthranilic acid 3,4‐dioxygenase (3HAO) is a non‐heme ferrous extradiol dioxygenase in the kynurenine pathway from tryptophan. It catalyzes the conversion of 3‐hydroxyanthranilate (HAA) to quinolinic acid (QUIN), an endogenous neurotoxin, via the activation of N‐methyl‐D‐aspartate (NMDA) receptors and the precursor of NAD+ biosynthesis. The crystal structure of 3HAO from S. cerevisiae at 2.4 Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure represents the first eukaryotic 3HAO to be resolved. The enzyme forms homodimers, with two nickel binding sites per molecule. One of the bound nickel atoms occupies the proposed ferrous‐coordinated active site, which is located in a conserved double‐strand β‐helix domain. Examination of the structure reveals the participation of a series of residues in catalysis different from other extradiol dioxygenases. Together with two iron‐binding residues (His49 and Glu55), Asp120, Asn51, Glu111, and Arg114 form a hydrogen‐bonding network; this hydrogen‐bond network is key to the catalysis of 3HAO. Residues Arg101, Gln59, and the substrate‐binding hydrophobic pocket are crucial for substrate specificity. Structure comparison with 3HAO from Ralstonia metallidurans reveals similarities at the active site and suggests the same catalytic mechanism in prokaryotic and eukaryotic 3HAO. Based on sequence comparison, we suggest that bicupin of human 3HAO is the first example of evolution from a monocupin dimer to bicupin monomer in the diverse cupin superfamilies. Based on the model of the substrate HAA at the active site of Y3HAO, we propose a mechanism of catalysis for 3HAO.
• Malherbe P.; Kohler C.; da Prada M., J Biol Chem, 1994, 0021-9258, 13792-7
  作者：Malherbe P.、Kohler C.、da Prada M.、Lang G.、Kiefer V.、Schwarcz R.、Lahm H.、Cesura A.M.

  DOI：——

  日期：——