6GIU

Human IMPase with L-690330

6GIU の概要

• エントリーDOI: 10.2210/pdb6giu/pdb
• 分子名称: Inositol monophosphatase 1, MANGANESE (II) ION, [1-(4-oxidanylphenoxy)-1-phosphono-ethyl]phosphonic acid, ... (5 entities in total)
• 機能のキーワード: impase, complex, lithium, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63170.16

構造登録者

Kraft, L.V.,Roe, S.M. (登録日: 2018-05-15, 公開日: 2018-10-17, 最終更新日: 2024-01-17)

主引用文献

Kraft, L.,Roe, S.M.,Gill, R.,Atack, J.R.
Co-crystallization of human inositol monophosphatase with the lithium mimetic L-690,330.
Acta Crystallogr D Struct Biol, 74:973-978, 2018

PubMed Abstract: Lithium, which is still the gold standard in the treatment of bipolar disorder, has been proposed to inhibit inositol monophosphatase (IMPase) and is hypothesized to exert its therapeutic effects by attenuating phosphatidylinositol (PI) cell signalling. Drug-discovery efforts have focused on small-molecule lithium mimetics that would specifically inhibit IMPase without exhibiting the undesired side effects of lithium. L-690,330 is a potent bisphosphonate substrate-based inhibitor developed by Merck Sharp & Dohme. To aid future structure-based inhibitor design, determination of the exact binding mechanism of L-690,330 to IMPase was of interest. Here, the high-resolution X-ray structure of human IMPase in complex with L690,330 and manganese ions determined at 1.39 Å resolution is reported.

PubMed: 30289407
DOI: 10.1107/S2059798318010380

実験手法

X-RAY DIFFRACTION (1.39 Å)