5AES

Crystal Structure of murine Chronophin (Pyridoxal Phosphate Phosphatase) in Complex with a PNP-derived Inhibitor

5AES の概要

• エントリーDOI: 10.2210/pdb5aes/pdb
• 分子名称: PYRIDOXAL PHOSPHATE PHOSPHATASE, MAGNESIUM ION, {2-[5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]ethyl}phosphonic acid, ... (5 entities in total)
• 機能のキーワード: hydrolase, pdxp, plpp, haloacid dehalogenase, had phosphatase, had hydrolase
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE)
• 細胞内の位置: Cytoplasm, cytosol : P60487
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63864.93

構造登録者

Knobloch, G.,Jabari, N.,Koehn, M.,Gohla, A.,Schindelin, H. (登録日: 2015-01-09, 公開日: 2015-04-01, 最終更新日: 2024-10-23)

主引用文献

Knobloch, G.,Jabari, N.,Stadlbauer, S.,Schindelin, H.,Kohn, M.,Gohla, A.
Synthesis of Hydrolysis-Resistant Pyridoxal 5'-Phosphate Analogs and Their Biochemical and X-Ray Crystallographic Characterization with the Pyridoxal Phosphatase Chronophin.
Bioorg.Med.Chem., 23:2819-, 2015

PubMed Abstract: A set of phosphonic acid derivatives (1-4) of pyridoxal 5'-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with an IC50 value of 79μM, which was in the range of the Km of the physiological substrate PLP. We also report the X-ray crystal structure of PDXP bound to compound 3, which we solved to 2.75Å resolution (PDB code 5AES). The co-crystal structure proves that compound 3 binds in the same orientation as PLP, and confirms the mode of inhibition to be competitive. Thus, we identify compound 1 as a PDXP phosphatase inhibitor. Our results suggest a strategy to design new, potent and selective PDXP inhibitors, which may be useful to increase the sensitivity of tumor cells to treatment with cytotoxic agents.

PubMed: 25783190
DOI: 10.1016/J.BMC.2015.02.049

実験手法

X-RAY DIFFRACTION (2.751 Å)