Crystal structure of single-domain VL of an anti-DNA binding antibody 3D8 scFv and its active site revealed by complex structures of a small molecule and metals

Suk-Youl Park; Woo-Ram Lee; Suk-Chan Lee; Myung-Hee Kwon; Yong-Sung Kim; Jeong-Sun Kim

doi:10.1002/prot.22011

Crystal structure of single-domain VL of an anti-DNA binding antibody 3D8 scFv and its active site revealed by complex structures of a small molecule and metals

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.22011 ◽

2008 ◽

Vol 71 (4) ◽

pp. 2091-2096 ◽

Cited By ~ 14

Author(s):

Suk-Youl Park ◽

Woo-Ram Lee ◽

Suk-Chan Lee ◽

Myung-Hee Kwon ◽

Yong-Sung Kim ◽

...

Keyword(s):

Crystal Structure ◽

Dna Binding ◽

Small Molecule ◽

Active Site ◽

Single Domain ◽

Complex Structures ◽

3D8 Scfv ◽

Binding Antibody

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Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase)

10.1101/2020.07.08.193284 ◽

2020 ◽

Author(s):

Gareth D. Fenn ◽

Helen Waller-Evans ◽

John R. Atack ◽

Benjamin D. Bax

Keyword(s):

Crystal Structure ◽

Bipolar Disorder ◽

Clinical Trials ◽

Small Molecule ◽

Murine Model ◽

Active Site ◽

Inositol Monophosphatase ◽

Allosteric Inhibitor ◽

Efficacious Treatment ◽

Partner Proteins

AbstractInositol 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 1.47Å 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.SynopsisHere we present a 1.47Å crystal structure of human inositol monophosphatase (IMPase) bound to the inhibitor ebselen (PDB entry 6ZK0). In the structure, ebselen forms a seleno-sulfide bond with cysteine 141 and ebselen-mediated contacts between two dimers give a ∼222 tetramer.

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Crystallization and structure of ebselen bound to Cys141 of human inositol monophosphatase

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x20011310 ◽

2020 ◽

Vol 76 (10) ◽

pp. 469-476

Author(s):

Gareth D. Fenn ◽

Helen Waller-Evans ◽

John R. Atack ◽

Benjamin D. Bax

Keyword(s):

Crystal Structure ◽

Bipolar Disorder ◽

Clinical Trials ◽

Small Molecule ◽

Murine Model ◽

Active Site ◽

Inositol Monophosphatase ◽

Allosteric Inhibitor ◽

Efficacious Treatment ◽

Partner Proteins

Inositol monophosphatase (IMPase) is inhibited by lithium, which is 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, the crystallization and the first structure of human IMPase covalently complexed with ebselen, a 1.47 Å resolution crystal structure (PDB entry 6zk0), are presented. In the complex with human IMPase, 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 approximate 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.

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