An activator for pyruvoyl-dependent l-aspartate α-decarboxylase is conserved in a small group of the γ-proteobacteria including Escherichia coli.

An activator for pyruvoyl-dependent l-aspartate α-decarboxylase is conserved in a small group of the γ-proteobacteria including Escherichia coli.
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DOI:
10.1002/mbo3.34
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发表时间:
2012-09
期刊:
影响因子:
3.4
通讯作者:
Niki, Hironori
Niki, Hironori
中科院分区:
生物学3区
文献类型:
--
作者:
Nozaki, Shingo;Webb, Michael E.;Niki, Hironori

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在细菌中,β-丙氨酸是通过L-天冬氨酸α-脱羧酶(PanD)的作用形成的,PanD是一种小类的天冬酰依赖性酶。这些酶中的乙酰基辅因子是通过肽骨架中丝氨酸残基的分子内重排形成的,导致链裂解并从丝氨酸残基形成共价结合的辅因子。该反应以前被认为是非催化的。在这里,我们表明,在大肠杆菌中,PanD被激活的假定乙酰转移酶YhhK,随后被称为PanZ。PanD在体内和体外的激活都是PanZ依赖性的。PanZ与PanD结合,我们证明了PanZ(N45 A)定点突变体无法增强PanD酶原的切割,尽管保留了对PanD的亲和力。这表明PanZ的推定乙酰转移酶结构域可能负责激活以增强PanD的加工。虽然panD在大多数细菌中是保守的,但panZ基因仅在E.大肠杆菌相关的肠细菌物种,包括志贺氏菌、沙门氏菌、克雷伯氏菌和耶尔森氏菌。这些细菌主要存在于肠道植物群中,其中泛酸丰富,PanZ对PanD的调节允许这些生物体响应代谢需求密切调节β-丙氨酸的产生,从而调节泛酸的产生。
In bacteria, β-alanine is formed via the action of l-aspartate α-decarboxylase (PanD) which is one of the small class of pyruvoyl-dependent enzymes. The pyruvoyl cofactor in these enzymes is formed via the intramolecular rearrangement of a serine residue in the peptide backbone leading to chain cleavage and formation of the covalently-bound cofactor from the serine residue. This reaction was previously thought to be uncatalysed. Here we show that in Escherichia coli, PanD is activated by the putative acetyltransferase YhhK, subsequently termed PanZ. Activation of PanD both in vivo and in vitro is PanZ-dependent. PanZ binds to PanD, and we demonstrate that a PanZ(N45A) site-directed mutant is unable to enhance cleavage of the proenzyme PanD despite retaining affinity for PanD. This suggests that the putative acetyltransferases domain of PanZ may be responsible for activation to enhance the processing of PanD. Although panD is conserved among most bacteria, the panZ gene is conserved only in E. coli-related enterobacterial species including Shigella, Salmonella, Klebsiella and Yersinia. These bacteria are found predominantly in the gut flora where pantothenate is abundant and regulation of PanD by PanZ allows these organisms to closely regulate production of β-alanine and hence pantothenate in response to metabolic demand.
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