Journal:Acta Cryst F:S2053230X20011310
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===Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase).=== | ===Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase).=== | ||
<big>Gareth D. Fenn, Helen Waller-Evans, John R. Atack and Benjamin D. Bax</big> <ref>doi 10.1107/S2053230X20011310</ref> | <big>Gareth D. Fenn, Helen Waller-Evans, John R. Atack and Benjamin D. Bax</big> <ref>doi 10.1107/S2053230X20011310</ref> | ||
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Inositol monophosphatase (IMPase) is inhibited by lithium, the most efficacious treatment for bipolar disorder. Several therapies have been approved, or are going through clinical trials, aimed at the replacement of lithium in the treatment of bipolar disorder. One candidate small molecule is ebselen, a selenium-containing antioxidant, which has been demonstrated to produce lithium-like effects, both in a murine model and in clinical trials. | Inositol monophosphatase (IMPase) is inhibited by lithium, the most efficacious treatment for bipolar disorder. Several therapies have been approved, or are going through clinical trials, aimed at the replacement of lithium in the treatment of bipolar disorder. One candidate small molecule is ebselen, a selenium-containing antioxidant, which has been demonstrated to produce lithium-like effects, both in a murine model and in clinical trials. | ||
| - | Here we present the crystallization and first structure of human IMPase covalently complexed with ebselen, a 1. | + | Here we present the crystallization and first structure of human IMPase covalently complexed with ebselen, a 1.47 Å crystal structure (PDB entry [[6zk0]]). In the human-IMPase-complex ebselen, in a ring opened conformation, is covalently attached to Cys141, a residue located away from the active site. |
IMPase is a dimeric enzyme and, in the crystal structure, two adjacent dimers share four ebselen molecules, creating a tetramer with ~222 symmetry. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins. | IMPase is a dimeric enzyme and, in the crystal structure, two adjacent dimers share four ebselen molecules, creating a tetramer with ~222 symmetry. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins. | ||
Revision as of 12:20, 19 August 2020
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