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Co-crystallization of human inositol monophosphatase with the lithium mimetic L-690,330
journal contribution
posted on 2023-06-09, 16:37 authored by L Kraft, M Roe, R Gill, J R AtackLithium, 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.
History
Publication status
- Published
File Version
- Published version
Journal
Acta Crystallographica Section D: Structural BiologyISSN
0907-4449Publisher
International Union of CrystallographyExternal DOI
Volume
74Page range
973-978Department affiliated with
- Biochemistry Publications
Research groups affiliated with
- Sussex Drug Discovery Centre Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2019-01-23First Compliant Deposit (FCD) Date
2019-01-22Usage metrics
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