Structural basis for nucleotide recognition by the ectoenzyme CD203c
Structural basis for nucleotide recognition by the ectoenzyme CD203c
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DOI：
10.1111/febs.14489
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发表时间：
2018-07-01
期刊：
影响因子：
5.4
通讯作者：
Nagar, Bhushan
中科院分区：
文献类型：
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作者：
Gorelik, Alexei;Randriamihaja, Antsa;Nagar, Bhushan
外核苷酸焦磷酸酶/磷酸二酯酶（NPP）家族通过降解细胞外核苷酸来调节嘌呤能信号传导。CD 203 c（NPP 3，ENPP 3）通过ATP水解调节嗜碱性粒细胞的炎症反应，是这些细胞表面过敏原敏感性的标志物。还提出了该蛋白质的多种其他作用和底物。为了深入了解其分子功能，我们确定了人NPP 3的晶体结构以及其与ATP类似物的复合物。该酶对核碱基类型几乎没有偏好，并与其配体的α和β磷酸基团形成特异性接触。蛋白质的二聚化不影响其催化活性。这些发现扩展了我们对NPP家族中底物识别的理解。数据库结构数据可在蛋白质数据库中获得，登录号为（human NPP 3）和（human NPP 3 T205 A N594 S with AMPCPP）。
The ecto-nucleotide pyrophosphatase/phosphodiesterase (NPP) enzyme family modulates purinergic signaling by degrading extracellular nucleotides. CD203c (NPP3, ENPP3) regulates the inflammatory response of basophils via ATP hydrolysis and is a marker for allergen sensitivity on the surface of these cells. Multiple other roles and substrates have also been proposed for this protein. In order to gain insight into its molecular functions, we determined the crystal structure of human NPP3 as well as its complex with an ATP analog. The enzyme exhibits little preference for nucleobase type, and forms specific contacts with the alpha and beta phosphate groups of its ligands. Dimerization of the protein does not affect its catalytic activity. These findings expand our understanding of substrate recognition within the NPP family.DatabaseStructural data are available in the Protein Data Bank under the accession numbers (human NPP3) and (human NPP3 T205A N594S with AMPCPP).