Structure and function of amino acid ammonia-lyases
Structure and function of amino acid ammonia-lyases
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DOI：
10.1080/10242420410001703496
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发表时间：
2004-03-01
影响因子：
1.8
通讯作者：
Rice, D
中科院分区：
文献类型：
--
作者：
Asano, Y;Kato, Y;Rice, D
组氨酸氨裂解酶 (HAL) 和甲基天冬氨酸氨裂解酶 (MAL) 属于碳氮裂解酶家族 (EC 4.3.1)。这些酶分别催化氨从 (S )-His α,β-消除产生尿刊酸，以及 (S)-苏式-(2 S, 3 S)-3-甲基天冬氨酸产生中康酸。根据结构分析，来自恶臭假单胞菌的 HAL 活性中心的肽被认为是翻译后脱水形成亲电的 4-亚甲基-咪唑-酮 (MIO) 基团。结合该结构提出了反应机理。另一方面，来自无丙二酸柠檬酸杆菌的MAL结构被发现是典型的TIM桶状结构，其中Mg2+与底物甲基天冬氨酸的4-羰基配位。与 HAL 不同，MAL 中没有观察到 MIO，并且 MAL 的反应似乎与苯丙氨酸氨裂解酶 (PAL)、HAL 和其他氨基酸氨裂解酶完全不同。提出了一种反应机理，其中底物氨基β位的氢被夺取，形成烯醇化物型中间体，然后释放出氨。
Histidine ammonia-lyase (HAL) and methylaspartate ammonia-lyase (MAL) belong to the family of carbon-nitrogen lyases (EC 4.3.1). The enzymes catalyze the alpha,beta-elimination of ammonia from (S )-His to yield urocanic acid, and (S)-threo -(2 S, 3 S)-3-methylaspartic acid to mesaconic acid, respectively. Based on structural analyses, the peptide at the active center of HAL from Pseudomonas putida is considered to be post-translationally dehydrated to form an electrophilic 4-methylidene-imidazole-one (MIO) group. A reaction mechanism was proposed with the structure. On the other hand, the structure of MAL from Citrobacter amalonaticus was found to be a typical TIM barrel structure with Mg2+ coordinated to the 4-carbonyl of the substrate methylaspartate. Unlike HAL, MIO was not observed in MAL, and the reaction of MAL appears to be completely different from phenylalanine ammonia-lyase (PAL), HAL, and other amino acid ammonia-lyases. A reaction mechanism is proposed in which the hydrogen at the beta to the amino group of the substrate is abstracted forming an enolate type intermediate and then ammonia is released.