Crystal Structure and Enzymology of Solanum tuberosum Inositol Tris/Tetrakisphosphate Kinase 1 (StITPK1).
Crystal Structure and Enzymology of Solanum tuberosum Inositol Tris/Tetrakisphosphate Kinase 1 (StITPK1).
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DOI：
10.1021/acs.biochem.3c00404
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发表时间：
2024-01-02
期刊：
影响因子：
2.9
通讯作者：
Brearley, Charles A.
中科院分区：
文献类型：
--
作者：
Whitfield, Hayley L.;Rodriguez, Raquel Faba;Shipton, Megan L.;Li, Arthur W. H.;Riley, Andrew M.;Potter, Barry V. L.;Hemmings, Andrew M.;Brearley, Charles A.
肌醇磷酸盐及其焦磷酸化衍生物对磷酸盐供应有反应，并且是磷酸盐体内平衡和生理学其他方面的试剂。这似乎是可能的酶，相互转换这些信号的工作对竞争底物和产品的混合群体的流行环境。肌醇焦磷酸的合成在植物中由两类ATP-抓握折叠激酶介导：PPIP5激酶，称为VIH，和肌醇三/四磷酸激酶（ITPK）家族的成员，特别是ITPK 1/2。ITPK1/2对植物中肌醇焦磷酸合成和周转的贡献的分子解释是不完整的：在已发表的晶体结构中没有核苷酸限制了对磷酸转移反应的解释，并且对ITPK1的潜在底物和竞争对手的亲和力知之甚少。在此，我们以2.26 Å的分辨率描述了ADP和StITPK 1的复合物，并使用简单的荧光偏振方法来比较不同的磷酸肌醇、焦磷酸肌醇和类似物的结合亲和力。通过简单的HPLC，我们揭示了ITPK 1的新的催化能力，不同的肌醇焦磷酸和显示的Ins（3，4，5，6）P4是一个有效的抑制剂肌醇焦磷酸合成活性的ITPK 1。我们进一步描述了精致的特异性ITPK1肌异构体之间的天然存在的肌醇六磷酸。
Inositol phosphates and their pyrophosphorylated derivatives are responsive to the phosphate supply and are agents of phosphate homeostasis and other aspects of physiology. It seems likely that the enzymes that interconvert these signals work against the prevailing milieu of mixed populations of competing substrates and products. The synthesis of inositol pyrophosphates is mediated in plants by two classes of ATP-grasp fold kinase: PPIP5 kinases, known as VIH, and members of the inositol tris/tetrakisphosphate kinase (ITPK) family, specifically ITPK1/2. A molecular explanation of the contribution of ITPK1/2 to inositol pyrophosphate synthesis and turnover in plants is incomplete: the absence of nucleotide in published crystal structures limits the explanation of phosphotransfer reactions, and little is known of the affinity of potential substrates and competitors for ITPK1. Herein, we describe a complex of ADP and StITPK1 at 2.26 Å resolution and use a simple fluorescence polarization approach to compare the affinity of binding of diverse inositol phosphates, inositol pyrophosphates, and analogues. By simple HPLC, we reveal the novel catalytic capability of ITPK1 for different inositol pyrophosphates and show Ins(3,4,5,6)P4 to be a potent inhibitor of the inositol pyrophosphate-synthesizing activity of ITPK1. We further describe the exquisite specificity of ITPK1 for the myo-isomer among naturally occurring inositol hexakisphosphates.
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肌醇 (1,3,4) 三磷酸酯 5/6 激酶 1 依赖性肌醇多磷酸调节拟南芥中的生长素反应。
影响因子：
7.4
作者：
Laha, Nargis Parvin;Giehl, Ricardo F. H.;Riemer, Esther;Qiu, Danye;Pullagurla, Naga Jyothi;Schneider, Robin;Dhir, Yashika Walia;Yadav, Ranjana;Mihiret, Yeshambel Emewodih;Gaugler, Philipp;Gaugler, Verena;Mao, Haibin;Zheng, Ning;von Wiren, Nicolaus;Saiardi, Adolfo;Bhattacharjee, Saikat;Jessen, Henning J.;Laha, Debabrata;Schaaf, Gabriel
通讯作者：
Schaaf, Gabriel
影响因子：
6.2
作者：
Gulabani, Hitika;Goswami, Krishnendu;Bhattacharjee, Saikat
通讯作者：
Bhattacharjee, Saikat
影响因子：
3.5
作者：
Caddick, Samuel E. K.;Harrison, Christopher J.;Brearley, Charles A.
通讯作者：
Brearley, Charles A.
影响因子：
7.2
作者：
Murphy, Alex M.;Otto, Bettina;Hanke, David E.
通讯作者：
Hanke, David E.
影响因子：
7.2
作者：
Desai, Mintu;Rangarajan, Padma;Gillaspy, Glenda E.
通讯作者：
Gillaspy, Glenda E.