[1-(14)C]-L-arginine | 289679-77-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: [1-(14)C]-L-arginine
• 英文别名: [1-(14)C]-L-Arg-OH；(2S)-2-amino-5-(diaminomethylideneamino)(114C)pentanoic acid
• CAS: 289679-77-2
• 化学式: C₆H₁₄N₄O₂
• 分子量: 176.192
• InChiKey: ODKSFYDXXFIFQN-QRTGCQPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.2
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [1-(14)C]-L-arginine 在 alpha-酮戊二酸 、 recombinant Giardia lamblia arginine deiminase 、 水 、 还原型辅酶Ⅰ 作用下， 生成 [1-(14)C]-L-citrulline
  参考文献：
  名称：

  Mechanisms of catalysis and inhibition operative in the arginine deiminase from the human pathogen Giardia lamblia

  摘要：

  Giardia lamblia arginine deiminase (GlAD), the topic of this paper, belongs to the hydrolase branch of the guanidine-modifying enzyme superfamily, whose members employ Cys-mediated nucleophilic catalysis to promote deimination of L-arginine and its naturally occurring derivatives. G. lamblia is the causative agent in the human disease giardiasis. The results of RNAi/antisense RNA gene-silencing studies reported herein indicate that GlAD is essential for G. lamblia trophozoite survival and thus, a potential target for the development of therapeutic agents for the treatment of giardiasis. The homodimeric recombinant protein was prepared in Escherichia coli for in-depth biochemical characterization. The 2-domain GlAD monomer consists of a N-terminal domain that shares an active site structure (depicted by an in silico model) and kinetic properties (determined by steady-state and transient state kinetic analysis) with its bacterial AD counterparts, and a C-terminal domain of unknown fold and function. GlAD was found to be active over a wide pH range and to accept L-arginine, L-arginine ethyl ester, N-alpha-benzoyl-L-arginine, and N-omega-amino-L-arginine as substrates but not agmatine, L-homoarginine, N-alpha-benzoyl- L-arginine ethyl ester or a variety of arginine-containing peptides. The intermediacy of a Cys424-alkylthiouronium ion covalent enzyme adduct was demonstrated and the rate constants for formation (k(1) = 80 s(-1)) and hydrolysis (k(2) = 35 s(-1)) of the intermediate were determined. The comparatively lower value of the steady-state rate constant (k(cat) = 2.6 s(-1)), suggests that a step following citrulline formation is rate-limiting. Inhibition of GlAD using Cys directed agents was briefly explored. S-Nitroso-L-homocysteine was shown to be an active site directed, irreversible inhibitor whereas N omega-cyano-L-arginine did not inhibit GlAD but instead proved to be an active site directed, irreversible inhibitor of the Bacillus cereus AD. (C) 2009 Published by Elsevier Inc.

  DOI：

  10.1016/j.bioorg.2009.06.001