Structure, function, and mechanism of proline utilization A (PutA).
Structure, function, and mechanism of proline utilization A (PutA).
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DOI：
10.1016/j.abb.2017.07.005
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发表时间：
2017-10-15
影响因子：
3.9
通讯作者：
Tanner JJ
中科院分区：
文献类型：
--
作者：
Liu LK;Becker DF;Tanner JJ
脯氨酸在多种生物过程中具有重要作用，例如细胞生物能量学、细胞生长、氧化和渗透应激反应、蛋白质折叠和稳定性以及氧化还原信号传导。脯氨酸分解代谢途径形成谷氨酸，使生物体能够利用脯氨酸作为碳、氮和能量来源。FAD依赖性脯氨酸脱氢酶（PRODH）和NAD+依赖性谷氨酸半醛脱氢酶（GSALDH）在两个连续的氧化步骤中将脯氨酸转化为谷氨酸。人类PRODH和GSALDH的消耗导致高脯氨酸血症，这与精神障碍如精神分裂症有关。此外，一些病原体需要脯氨酸催化剂来产生毒力。脯氨酸催化剂的一个独特方面是在革兰氏阴性菌中发现的多功能脯氨酸利用A（PutA）酶。PutA是一种大的（> 1000个残基）双功能酶，其将PRODH和GSALDH活性结合到一条多肽链中。此外，一些PutA作为脯氨酸利用基因的DNA结合转录阻遏物起作用。本文综述了PutA的几个属性，使其成为一个显着的黄素酶：（1）寡聚体状态和四级结构的多样性;（2）底物通道和酶滞后;（3）DNA结合活性和转录抑制功能;（4）黄素氧化还原依赖的变化，亚细胞的位置和功能响应脯氨酸（功能开关）。
Proline has important roles in multiple biological processes such as cellular bioenergetics, cell growth, oxidative and osmotic stress response, protein folding and stability, and redox signaling. The proline catabolic pathway, which forms glutamate, enables organisms to utilize proline as a carbon, nitrogen, and energy source. FAD-dependent proline dehydrogenase (PRODH) and NAD+-dependent glutamate semialdehyde dehydrogenase (GSALDH) convert proline to glutamate in two sequential oxidative steps. Depletion of PRODH and GSALDH in humans leads to hyperprolinemia, which is associated with mental disorders such as schizophrenia. Also, some pathogens require proline catabolism for virulence. A unique aspect of proline catabolism is the multifunctional proline utilization A (PutA) enzyme found in Gram-negative bacteria. PutA is a large (> 1000 residues) bifunctional enzyme that combines PRODH and GSALDH activities into one polypeptide chain. In addition, some PutAs function as a DNA-binding transcriptional repressor of proline utilization genes. This review describes several attributes of PutA that make it a remarkable flavoenzyme: (1) diversity of oligomeric state and quaternary structure; (2) substrate channeling and enzyme hysteresis; (3) DNA-binding activity and transcriptional repressor function; and (4) flavin redox dependent changes in subcellular location and function in response to proline (functional switching).
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影响因子：
4
作者：
Arentson BW;Hayes EL;Zhu W;Singh H;Tanner JJ;Becker DF
通讯作者：
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影响因子：
2.9
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通讯作者：
Gascuel O