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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 Atack
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Acta Crystallographica Section D: Structural Biology

ISSN

0907-4449

Publisher

International Union of Crystallography

Volume

74

Page range

973-978

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Sussex Drug Discovery Centre Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2019-01-23

First Compliant Deposit (FCD) Date

2019-01-22

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