Synthesis of hydrolysis-resistant pyridoxal 5'-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin.
作者： Gunnar Knobloch , Nauras Jabari , Sven Stadlbauer , Hermann Schindelin , Maja Köhn
DOI: 10.1016/J.BMC.2015.02.049
关键词:
摘要: Abstract A set of phosphonic acid derivatives ( 1 – 4 ) pyridoxal 5′-phosphate (PLP) was synthesized and characterized biochemically using purified murine phosphatase (PDXP), also known as chronophin. The most promising compound displayed primarily competitive PDXP inhibitory activity with an IC 50 value 79 μM, which in the range K m physiological substrate PLP. We report X-ray crystal structure bound to 3 , we solved 2.75 A resolution (PDB code 5AES). co-crystal proves that binds same orientation PLP, confirms mode inhibition be competitive. Thus, identify a inhibitor. Our results suggest strategy design new, potent selective inhibitors, may useful increase sensitivity tumor cells treatment cytotoxic agents.
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