Abstract：
Biotin-dependent carboxylases are widely distributed in nature and have central roles in the metabolism of fatty acids, amino acids, carbohydrates, and other compounds. The last decade has seen the accumulation of structural information on most of these large holoenzymes, including the 500-kDa dimeric yeast acetyl-CoA carboxylase, the 750-kDa α6β6 dodecameric bacterial propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, and geranyl-CoA carboxylase, the 720-kDa hexameric bacterial long-chain acyl-CoA carboxylase, the 500-kDa tetrameric bacterial single-chain pyruvate carboxylase, the 370-kDa α2β4 bacterial two-subunit pyruvate carboxylase, and the 130-kDa monomeric eukaryotic urea carboxylase. A common theme that has emerged from these studies is the dramatic structural flexibility of these holoenzymes despite their strong overall sequence conservation, evidenced both by the extensive diversity in the architectures of the holoenzymes and by the extensive conformational variability of their domains and subunits. This structural flexibility is crucial for the function and regulation of these enzymes and identifying compounds that can interfere with it represents an attractive approach for developing novel modulators and drugs. The extensive diversity observed in the structures so far and its biochemical and functional implications will be the focus of this review.
摘要：
生物素依赖性羧化酶在自然界中广泛分布，在脂肪酸代谢中起着核心作用，氨基酸,碳水化合物,和其他化合物。在过去的十年中，大多数这些大型全酶的结构信息都在积累，包括500kDa二聚酵母乙酰辅酶A羧化酶，750-kDaα6β6十二聚体细菌丙酰辅酶A羧化酶，3-甲基巴豆酰辅酶A羧化酶，和香叶酰辅酶A羧化酶，720-kDa六聚体细菌长链酰基辅酶A羧化酶，500kDa四聚体细菌单链丙酮酸羧化酶，370-kDaα2β4细菌双亚基丙酮酸羧化酶，和130-kDa单体真核脲羧化酶。从这些研究中出现的一个共同主题是这些全酶的戏剧性结构灵活性，尽管它们具有很强的整体序列保守性，全酶结构的广泛多样性以及其域和亚基的广泛构象变异性都证明了这一点。这种结构灵活性对于这些酶的功能和调节是至关重要的,并且鉴定可以干扰它的化合物代表了开发新的调节剂和药物的有吸引力的方法。到目前为止，在结构中观察到的广泛多样性及其生化和功能影响将是这篇综述的重点。
