The Ligand Binding Region of the Sigma-1 Receptor: Studies Utilizing Photoaffinity Probes, Sphingosine and N-Alkylamines

Author(s): Arnold E. Ruoho, Uyen B. Chu, Subramaniam Ramachandran, Dominique Fontanilla, Timur Mavlyutov, Abdol R. Hajipour.

Journal Name: Current Pharmaceutical Design

Volume 18 , Issue 7 , 2012

Abstract:

The sigma-1 receptor is a 26 kDa endoplasmic reticulum resident membrane protein that has been shown to have chaperone activity in addition to its promiscuous binding to pharmacological agents. Ligand binding domain(s) of the sigma-1 receptor have been identified using the E. coli expressed and purified receptor protein and novel radioiodinated azido photoaffinity probes followed by proteolytic and chemical cleavage strategies. The outcome of these experiments indicates that the sigma-1 receptor ligand binding regions are formed primarily by juxtaposition of its second and third hydrophobic domains, regions where the protein shares considerable homology with the fungal enzyme, sterol isomerase that is essential for the biosynthesis of ergosterol. Data indicate that these hydrophobic steroid binding domain like (SBDL) regions on the sigma-1 receptor are likely to interact selectively with N-alkyl amines such as the endogenous sphingolipids and with synthetic N-alkylamines and N-aralkylamines derivatives. A proposed model for the sigma-1 receptor is presented.

Keywords: Sigma-1 receptor, photoaffinity labeling, ligand binding region, shingosine, N-alkylamines, chaperone, yeast sterol isomerase, mutagenesis, oligodendrocytes, sphingosine

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 18
ISSUE: 7
Year: 2012
Page: [920 - 929]
Pages: 10
DOI: 10.2174/138161212799436584
Price: $65

Article Metrics

PDF: 17