EBP Membrane Protein Introduction

Introduction of EBP

EBP is encoded by the EBP gene, and is also known as 3-beta-hydroxysteroid-Delta(8), Delta(7)-isomerase, Cholestenol Delta-isomerase, Delta(8)-Delta(7) sterol isomerase, D8-D7 sterol isomerase and Emopamil-binding protein. EBP is a vertebrate sterol ∆8-∆7 isomerase which has demonstrated equal high binding affinity for both enantiomers of emopamil, a Ca²⁺ channel blocker. EBP characterization was achieved using the anti-ischemic drug (-)-(S)-emopamil. EBP catalyzes the shift of the double bond from C8-C9 to C7-C8 position in one of the last steps of cholesterol de novo biosynthesis.

Function of EBP Membrane Protein

EBP is a high-affinity receptor for the phenylalkylamine calcium-antagonist emopamil and other antiischaemic drugs. EBP was shown to be an enzyme of post-squalene cholesterol biosynthesis catalyzing the shift of a double bond in the B-ring of the sterol nucleus. EBP is a high-affinity binding protein for ^[3H]emopamil and belongs to the family of so-called sigma receptors. The isoenzyme of EBP from yeast, ERG2, is structurally diverse from EBP but is homologous with the sigma1 receptor, which interacts physically and functionally with InsP3 receptors and K⁺ channels. The pharmacological commonalities of EBP and ERG2 with sigma1 and sigma2 receptors suggested that EBP also belonged to the family of so-called sigma receptors. Meanwhile, EBP is localized on chromosome Xp11.23-p11.22 and is essential for cholesterol biosynthesis. Mutations in EBP cause X-chromosomal dominant chondrodysplasia punctate.

Fig.1 Transmembrane topology of EBP membrane protein (Sanchez, 2014).

Application of EBP Membrane Protein in Literature

1. Toyohara J., et al. Re-evaluation of in vivo selectivity of ^[11C]SA4503 to σ1 eceptors in the brain: Contributions of emopamil binding protein. Nuclear Medicine and Biology. 2012, 39(7):1049-1052. PubMed ID: 22497960
   
   

   Authors in this article assesse the in vivo blocking effects of selective σ1 receptor and EBP blockers on the brain uptake of ^[11C]SA4503 by the tissue dissection method at a single time point. The results indicated that the contribution of in vivo EBP binding of ^[11C]SA4503 was negligible in the mouse brain.

2. Ozyurt K., et al. (2015) Emopamil Binding Protein Mutation in Conradi-Hünermann-Happle Syndrome Representing Plaque-Type Psoriasis. Indian Journal of Dermatology. 2015, 60(2):216-216. PubMed ID: 25814754
   
   

   This article indicates that EBP is identified and associated with Conradi-Hünermann-Happle syndrome. Meanwhile, there are about 70 different mutations in the EBP gene have been described related to this disease.

3. Silve S., et al. Emopamil-binding protein, a mammalian protein that binds a series of structurally diverse neuroprotective agents, exhibits delta 8 - delta 7 sterol isomerase activity in yeast. J. Biol. Chem. 1996, 271(37):22434-22440. PubMed ID: 8798407
   
   

   The results of this article strongly suggest that EBP and delta 8-delta 7 sterol isomerase are identical proteins in mammals.

4. Berardi F., et al. Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ8−Δ7 Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity. J. Med. Chem. 2008, 51(23):7523-7531. PubMed ID: 19053780
   
   

   This article reports a novel class of EBP inhibitors, which represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well as a starting point for developing new anticancer drugs.

5. Moebius FF., et al. Cloning of an emopamil-binding protein (EBP)-like protein that lacks sterol delta8-delta7 isomerase activity. Biochem. J. 2003, 374(Pt 1):229-237. PubMed ID: 12760743
   
   

   The work of this article identifies and characterized EBPL, a novel microsomal protein that has neither detectable 3β-hydroxysteroid sterol 8-7 isomerase nor sigma-ligand-binding activity when expressed in yeast, despite a distant evolutionary relationship with EBP.

EBP Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Besides, aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-EBP antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

With extensive experience in membrane proteins, Creative Biolabs provides world-leading production service for our worldwide customers to help them to accomplish numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

1. Sanchez-Pulido L & Ponting CP. (2014) TM6SF2 and MAC30, new enzyme homologs in sterol metabolism and common metabolic disease. Frontiers in Genetics. 5:439.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.