Co‐crystallization of human inositol monophosphatase with the lithium mimetic L‐690,330

Kraft, L, Roe, M, Gill, R and Atack, J R (2018) Co‐crystallization of human inositol monophosphatase with the lithium mimetic L‐690,330. Acta Crystallographica Section D: Structural Biology, 74. pp. 973-978. ISSN 0907-4449

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Chemistry
Research Centres and Groups: Sussex Drug Discovery Centre
Depositing User: Raj Gill
Date Deposited: 23 Jan 2019 10:57
Last Modified: 02 Jul 2019 13:17
URI: http://sro.sussex.ac.uk/id/eprint/81427

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