Journal:Acta Cryst F:S2053230X20011310
From Proteopedia
(Difference between revisions)
| Line 5: | Line 5: | ||
<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
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. | ||
| + | |||
| + | View of ebselen attached to Cys141 (PDB entry [[6zk0]]): | ||
| + | *<scene name='85/859036/Cv/17'>Overview of two ebselen molecules attached to A and A' (symmetry related) subunits around crystallographic twofold axis</scene>. One subunit (A) has carbons in orange and the second (A') subunit has carbons slate-blue (nitrogens are blue, carbons red, seleniums orange and sulphurs gold). | ||
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. | 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. |
Orthogonal views of IMPase dimer showing ebselen on Cys141 and metal ions in the active sites based on the structure of PDB entry [[6zk0]]: | Orthogonal views of IMPase dimer showing ebselen on Cys141 and metal ions in the active sites based on the structure of PDB entry [[6zk0]]: | ||
Revision as of 14:28, 23 August 2020
| |||||||||||
This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
