L-Glutamine-β-naphthylamide | 735-82-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: L-Glutamine-β-naphthylamide
• 英文别名: Gln-β-naphthylamide；L-glutaminyl 2-naphthylamide；Gln-βNA；L-glutamine 2-naphthylamide；(2S)-2-amino-N-naphthalen-2-ylpentanediamide
• CAS: 735-82-0
• 化学式: C₁₅H₁₇N₃O₂
• 分子量: 271.319
• InChiKey: SCBLXQAXDOWFIH-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-Glutamine-β-naphthylamide 在 Xanthomonas campestris glutaminyl cyclase (XcGC) 作用下， 生成 L-焦谷氨酸
  参考文献：
  名称：

  Crystal Structure and Functional Analysis of the Glutaminyl Cyclase from Xanthomonas campestris

  摘要：

  Glutaminyl cyclases (QCs) (EC 2.3.2.5) catalyze the formation of pyroglutamate (pGlu) at the N-terminus of many proteins and peptides, a critical step for the maturation of these bioactive molecules. Proteins having QC activity have been identified ill animals and plants, but not in bacteria. Here, we report the first bacterial QC from the plant pathogen Xanthomonas campestris (Xc). The crystal structure of the enzyme was solved and refined to 1.44-angstrom resolution. The structure shows a five-bladed beta-propeller and exhibits a scaffold similar to that of papaya QC (pQC), but with some sequence deletions and conformational changes. In contrast to the pQC structure, the active site of XcQC has a wider substrate-binding pocket, but its accessibility is modulated by a protruding loop acting as a flap. Enzyme activity analyses showed that the wild-type XcQC possesses only 3% QC activity compared to that of pQC. Superposition of those two structures revealed that an active-site glutamine residue in pQC is substituted by a glutamate (Glu(45)) in XcQC, although position 45 is a glutamine in most bacterial QC sequences. The E45Q mutation increased the QC activity by an order of magnitude, but the mutation E45A led to a drop in the enzyme activity, indicating the critical catalytic role of this residue. Further mutagenesis studies support the catalytic role of Glu(89) as proposed previously and confirm the importance of several conserved amino acids around the substrate-binding pocket. XcQC was shown to be weakly resistant to guanidine hydrochloride, extreme pH, and heat denaturations, in contrast to the extremely high stability of pQC, despite their similar scaffold. On the basis of structure comparison, the low stability of XcQC may be attributed to the absence of both a disulfide linkage and some hydrogen bonds in the closure of beta-propeller structure. These results significantly improve our understanding of the catalytic mechanism and extreme stability of type I QCs, which will be useful in further applications of QC enzymes. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.jmb.2010.06.012

文献信息

• Strains of bacillus thuringiensis
  申请人：PLANT GENETIC SYSTEMS, N.V.

  公开号：EP0382990A1

  公开（公告）日：1990-08-22

  Two new Bacillus thuringiensis strains, which are deposited at the DSM under accession nos. 5131 and 5132, produce crystal proteins during sporulation that are toxic to Coleoptera. The crystal proteins contain 74 kDa and 129 kDa protoxins, respectively, which can yield 67 and 66 kDa toxins, respectively, as trypsin-digestion products. A plant, the genome of which is transformed with a DNA sequence that comes from either one of the strains and that codes for its respective toxin, is resistant to Coleoptera. Each strain, itself, or its crystals, crystal proteins, protoxin or toxin can be used as the active ingredient in an insecticidal composition for combatting Coleoptera.

  两种新的苏云金芽孢杆菌菌株（存于 DSM，登录号分别为 5131 和 5132）在孢子化过程中会产生对鞘翅目昆虫有毒的晶体蛋白。晶体蛋白分别含有 74 kDa 和 129 kDa 的原毒素，作为胰蛋白酶消化产物，可分别产生 67 kDa 和 66 kDa 的毒素。植物的基因组经 DNA 序列转化后，对鞘翅目昆虫具有抗性。每种菌株本身或其晶体、晶体蛋白、原毒素或毒素都可用作防治鞘翅目昆虫的杀虫组合物的活性成分。
• In vivo screening models for treatment of Alzheimer's disease and other QPCT-related disorders
  申请人：Probiodrug AG

  公开号：EP2395095A1

  公开（公告）日：2011-12-14

  The present invention provides a transgenic non-human animal, in particular a transgenic mouse encoding Qpct proteins, which have been implicated in Qpct-related diseases. The present invention additionally provides cells and cell lines comprising transgenes encoding for Qpct. The present invention further provides methods and compositions for evaluating agents that affect Qpct, for use in compositions for the treatment of Qpct-related diseases.

  本发明提供了一种编码 Qpct 蛋白的转基因非人类动物，特别是转基因小鼠，Qpct 蛋白与 Qpct 相关疾病有关。本发明还提供了包含编码 Qpct 的转基因的细胞和细胞系。本发明进一步提供了评估影响 Qpct 的制剂的方法和组合物，用于治疗 Qpct 相关疾病的组合物中。
• Modified proteins, designer toxins, and methods of making thereof
  申请人：——

  公开号：US20030176331A1

  公开（公告）日：2003-09-18

  The present invention concerns methods of reducing the antigenicity of a proteinaceous compound while maintaining the compounds biological activity, as well as proteinaceous compositions with biological activity but reduced antigenicity. These methods and compositions have significant benefits to a subject in need of such compounds and compositions. Also included are modified toxin compounds that are truncated and/or possess reduce antigenicity. Such designer toxins have therapeutic, diagnostic, and preventative benefits, particularly as immunotoxins. Methods of treating cancer using these immunotoxins are provided.

  本发明涉及在保持蛋白质化合物生物活性的同时降低其抗原性的方法，以及具有生物活性但抗原性降低的蛋白质组合物。这些方法和组合物对需要此类化合物和组合物的受试者大有裨益。此外，还包括经修饰的毒素化合物，这些化合物被截短和/或抗原性降低。这种设计毒素具有治疗、诊断和预防作用，特别是作为免疫毒素。提供了使用这些免疫毒素治疗癌症的方法。
• Snake venom glutaminyl cyclases: Purification, cloning, kinetic study, recombinant expression, and comparison with the human enzyme
  作者：Ying-Ming Wang、Kai-Fa Huang、Inn-Ho Tsai

  DOI：10.1016/j.toxicon.2014.04.012

  日期：2014.8

  Among various snake venom components, glutaminyl cyclase (vQC) is one of the least understood protein family and none of its members has been purified or characterized. Here we confirmed the presence of vQC activity in a wide spectrum of venom species via enzymatic assay using a synthetic fluorogenic substrate. We have also cloned novel vQC cDNAs from seven species including Crotalus atrox. The results revealed more than 96% sequence similarities among vQCs and similar to 75% sequence identities between vQCs and human secretory QC (hQC). The vQC glycoprotein of 43 kDa was isolated from C atrox venom, and its N-terminal sequence was determined. The optimal pH range for vQC reaction was 7.5-8.0, and the enzymes were stable up to 50 degrees C. Similar to hQC, vQCs were substantially inactivated by 1 mM 1,10-phenanthroline but slightly affected by 20 mM EDTA, suggestive of a similar zinc-catalytic environment for these enzymes. Although their catalytic residues were highly conserved, vQCs were less susceptible to inhibition by synthetic imidazole derivatives which potently inhibited hQC. The 3D-models revealed that vQC and hQC structures display different surface charge distributions around the active sites, which might affect substrate and inhibitor binding affinities. The recombinant vQCs prepared from Escherichia colt displayed weaker substrate binding affinities relative to the native vQCs, possibly due to the lack of glycosylation. The present report offers new structural and functional insights into vQCs and sheds light on the specificity differences between vQCs and hQC. (C) 2014 Elsevier Ltd. All rights reserved.
• MODIFIED PROTEINS, DESIGNER TOXINS, AND METHODS OF MAKING THEREOF
  申请人：RESEARCH DEVELOPMENT FOUNDATION

  公开号：EP1406644A2

  公开（公告）日：2004-04-14