Structural and biochemical characterization of inorganic pyrophosphatase from Homo sapiens

Structural and biochemical characterization of inorganic pyrophosphatase from Homo sapiens
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智人无机焦磷酸酶的结构和生化特征

DOI:
10.1016/j.bbrc.2020.09.139
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发表时间:
2020-12-17
影响因子:
3.1
通讯作者:
Li, Lisheng
Li, Lisheng
中科院分区:
生物学4区
文献类型:
--
作者:
Hu, Fen;Huang, Zelong;Li, Lisheng

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无机焦磷酸酶(PPase)在能量守恒中起着重要作用,并为许多生物合成途径提供能量。在这里,我们提出了两个三维结构的PPase从智人(Hu-PPase)在2.38埃和3.40埃在不同的结晶条件。两个镁金属离子的Hu-PPase结构复合物中的一个被确定为单体(Hu-PPase-mono),而另一个被确定为二聚体-二聚体(Hu-PPase-dd)。在Hu-PPase-mono的每个不对称单元中,有4个α-螺旋和10个β-链,折叠成桶形结构,并且活性位点含有两个镁离子。像许多物种的PPase一样,我们发现Hu-PPase能够进行自组装。令我们惊讶的是,Hu-PPase自组装的破坏并不影响其酶活性或促进细胞生长的能力。我们的工作揭示了Hu-PPase的不同结构形式,发现Hu-PPase的焦磷酸酶活性与其自组装无关。(C)2020爱思唯尔公司All rights reserved.
Inorganic pyrophosphatase (PPase) plays an essential role in energy conservation and provides energy for many biosynthetic pathways. Here, we present two three-dimensional structures of PPase from Homo sapiens (Hu-PPase) at 2.38 angstrom and 3.40 angstrom in different crystallization conditions. One of the Hu-PPase structures complex of two magnesium metal ions was determined to be a monomer (Hu-PPase-mono) here, while the other one to be a dimer-dimer (Hu-PPase-dd). In each asymmetric unit of Hu-PPase-mono, there are four alpha-helices and ten beta-strands and folds as a barrel structure, and the active site contains two magnesium ions. Like PPases from many species, we found that Hu-PPase was able to undergo self-assembly. To our surprise, disruption of the self-assembly of Hu-PPase did not influence its enzymatic activity or the ability to promote cell growth. Our work uncovered that different structure forms of Hu-PPase and found that the pyrophosphatase activity of Hu-PPase is independent of its self-assembly. (C) 2020 Elsevier Inc. All rights reserved.