Loss of YggS (COG0325) impacts aspartate metabolism in Salmonella enterica.
Loss of YggS (COG0325) impacts aspartate metabolism in Salmonella enterica.
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DOI：
10.1111/mmi.14810
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发表时间：
2021-10
影响因子：
3.6
通讯作者：
Downs DM
中科院分区：
文献类型：
--
作者：
Vu HN;Downs DM
YggS是一种5′-磷酸吡哆醛（PLP）结合蛋白，属于保守的COG 0325家族。尽管在许多物种中与维生素B6体内平衡有关，但YggS如何有助于细胞功能的精确生物化学活性和分子机制都没有描述。在转座子诱变筛选中，我们发现在缺乏yggS的肠道沙门氏菌菌株中aspC（编码PLP依赖性天冬氨酸转氨酶，EC 2.6.1.1）中的插入引起合成生长缺陷，这可以通过添加外源性天冬氨酸来挽救。对改善yggS aspC双突变体生长的自发抑制因子的表征表明，这种合成天冬氨酸限制依赖于TyrB，TyrB是一种PLP依赖性芳香族氨基酸氨基转移酶（EC 2.6.1.57）。遗传和生化数据与TyrB活性被yggS突变引起的吡哆醇5′-磷酸和α-酮酸积累抑制的假设一致。本研究提供的数据与工作模型一致，该模型涉及YggS通过转氨作用调节B6维生素的浓度。在肠道沙门氏菌中，AspC和TyrB是能够催化谷氨酸-天冬氨酸转氨的吡哆醛5′-磷酸（PLP）依赖性转氨酶。在这里，我们表明，YggS，一个未表征的PLP结合蛋白的维生素B6的稳态牵连的损失，影响TyrB依赖的天冬氨酸合成。我们的数据表明，这种效应是由吡哆醇5′-磷酸（PNP）的积累和α-酮酸池的扰动介导的，如α-酮丁酸（αKB）和α-酮戊二酸（αKG），这是yggS突变的结果。
YggS is a pyridoxal 5′-phosphate (PLP)-binding protein of the conserved COG0325 family. Despite a connection with vitamin B6 homeostasis in many species, neither a precise biochemical activity nor molecular mechanism of how YggS contributes to cellular function has been described. In a transposon mutagenesis screen, we found that insertions in aspC (encoding a PLP-dependent aspartate aminotransferase, EC 2.6.1.1) in a Salmonella enterica strain lacking yggS caused a synthetic growth defect, which could be rescued by addition of exogenous aspartate. Characterization of spontaneous suppressors which improved growth of the yggS aspC double mutant suggested that this synthetic aspartate limitation was dependent on TyrB, a PLP-dependent aromatic-amino-acid aminotransferase (EC 2.6.1.57). Genetic and biochemical data were consistent with the hypothesis that TyrB activity was inhibited by accumulated pyridoxine 5′-phosphate and α-keto acids caused by a yggS mutation. This study provides data consistent with a working model implicating YggS in modulating concentrations of B6 vitamers via transamination. In Salmonella enterica, AspC and TyrB are pyridoxal 5′-phosphate (PLP)-dependent aminotransferases capable of catalyzing glutamate-aspartate transamination. Herein we show that loss of YggS, an uncharacterized PLP-binding protein implicated in vitamin B6 homeostasis, impacts TyrB-dependent aspartate synthesis. Our data suggest this effect is mediated by accumulation of pyridoxine 5′-phosphate (PNP) and perturbations of α-keto acids pool, such as α-ketobutyrate (αKB) and α-ketoglutarate (αKG), which are consequences of a yggS mutation.
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影响因子：
6.4
作者：
Glazyrina J;Materne EM;Dreher T;Storm D;Junne S;Adams T;Greller G;Neubauer P
通讯作者：
Neubauer P
影响因子：
14.8
作者：
Doucette, Christopher D.;Schwab, David J.;Wingreen, Ned S.;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
3.2
作者：
GELFAND, DH;STEINBERG, RA
通讯作者：
STEINBERG, RA
影响因子：
3.2
作者：
Martinez-Chavarria, Luary C.;Sagawa, Janelle;Vadyvaloo, Viveka
通讯作者：
Vadyvaloo, Viveka
影响因子：
--
作者：
Heath O;Pitt J;Mandelstam S;Kuschel C;Vasudevan A;Donoghue S
通讯作者：
Donoghue S