Crystal Structure of Sphingosine Kinase 1 with PF-543
Crystal Structure of Sphingosine Kinase 1 with PF-543
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DOI：
10.1021/ml5004074
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发表时间：
2014-12-01
影响因子：
4.2
通讯作者：
Elkins, Jonathan M.
中科院分区：
文献类型：
--
作者：
Wang, Jing;Knapp, Stefan;Elkins, Jonathan M.
目前发现的最有效的SPHK1抑制剂是PF-543。在1.8埃分辨率下，SPHK1与抑制剂PF-543配合物的晶体结构显示，抑制剂结合在弯曲构象中，类似于结合的鞘氨醇底物，但具有旋转的头基。所提出的结构数据将有助于设计具有改进性能的SPHK1和SPHK2抑制剂。
The most potent inhibitor of Sphingosine Kinase 1 (SPHK1) so far identified is PF-543. The crystal structure of SPHK1 in complex with inhibitor PF-543 to 1.8 angstrom resolution reveals the inhibitor bound in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group. The structural data presented will aid in the design of SPHK1 and SPHK2 inhibitors with improved properties.