Biology:Emopamil binding protein
 Generic protein structure example |
| 3-beta-hydroxysteroid-Δ8,Δ7-isomerase | |||||||||
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| Identifiers | |||||||||
| EC number | 5.3.3.5 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Emopamil binding protein is a protein that in humans is encoded by the EBP gene, located on the X chromosome.[1] EBP was discovered through its high-affinity binding to anti-ischemic drugs such as emopamil, from which it also derives its name. In addition to emopamil, EBP also bind with high affinity a variety of structurally unrelated compounds, such as amiodarone, opipramol, ifenprodil, trifluoperazine, and chlorpromazine.[2] EBP has a mass of 27.3 kDa and resembles the σ2-receptor that resides in the endoplasmic reticulum of various tissues as an integral membrane protein.[3]
Function
EBP functions as a Δ8–Δ7 sterol isomerase, catalyzing the migration of the double bond in the sterol B-ring from the 8(9) to the 7(8) position.[4] In the Bloch pathway of cholesterol biosynthesis, EBP converts zymosterol to dehydrolathosterol, while in the Kandutsch–Russell pathway it converts zymostenol to lathosterol. EBP catalyzes the conversion of zymostenol to lathosterol
Clinical significance
Mutations in EBP cause Conradi–Hünermann syndrome and impairs cholesterol biosynthesis.[5] Unborn males affected with EBP mutations are not expected to be liveborn, (with up to only 5% male births). Individuals, mostly female, that are liveborn with EBP mutations experience stunted growth, limb reduction and back problems. Later in life, the individual may develop cataracts along with coarse hair and hair loss.[6]
Research areas
Remyelination and MS
The inhibition of EBP promotes oligodendrocyte formation, which may help remyelination and thus limit multiple sclerosis development. [7]
Cloning
Isolation, replication and characterization of the EBP and EBP-like protein have been performed in yeast/E. Coli strains (which lack the EBP protein in nature) to study the high-affinity drug binding effects.[3]
See also
- Emopamil
- Cholestenol Delta-isomerase
- Sigma-1 receptor
- Sigma-2 receptor
References
- ↑ "Functional analysis of cholesterol biosynthesis by RNA interference". The Journal of Steroid Biochemistry and Molecular Biology 104 (3–5): 105–109. May 2007. doi:10.1016/j.jsbmb.2007.03.001. PMID 17498944.
- ↑ Moebius, F F; Hanner, M; Knaus, H G; Weber, F; Striessnig, J; Glossmann, H (November 1994). "Purification and amino-terminal sequencing of the high affinity phenylalkylamine Ca2+ antagonist binding protein from guinea pig liver endoplasmic reticulum.". Journal of Biological Chemistry 269 (46): 29314–29320. doi:10.1016/s0021-9258(19)62046-6.
- ↑ 3.0 3.1 "Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression". The Journal of Biological Chemistry 270 (13): 7551–7557. March 1995. doi:10.1074/jbc.270.13.7551. PMID 7706302.
- ↑ Silve, Sandra; Dupuy, Pascal Henry; Labit-Lebouteiller, Christine; Kaghad, Mourad; Chalon, Pascale; Rahier, Alain; Taton, Maryse; Lupker, Jan et al. (13 September 1996). "Emopamil-binding Protein, a Mammalian Protein That Binds a Series of Structurally Diverse Neuroprotective Agents, Exhibits Δ8-Δ7 Sterol Isomerase Activity in Yeast *". Journal of Biological Chemistry 271 (37): 22434–22440. doi:10.1074/jbc.271.37.22434. PMID 8798407.
- ↑ "A novel EBP c.224T>A mutation supports the existence of a male-specific disorder independent of CDPX2". American Journal of Medical Genetics. Part A 164A (7): 1642–1647. July 2014. doi:10.1002/ajmg.a.36508. PMID 24700572.
- ↑ "Chondrodysplasia Punctata". Obstetric Imaging: Fetal Diagnosis and Care (2nd ed.). Elsevier. 2018. pp. 259–261. doi:10.1016/b978-0-323-44548-1.00048-6. ISBN 978-0-323-44548-1.
- ↑ "Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation". Journal of Medicinal Chemistry 67 (6): 4819–4832. March 2024. doi:10.1021/acs.jmedchem.3c02396. PMID 38470227.
External links
- GeneReviews/NCBI/NIH/UW entry on Chondrodysplasia Punctata 2, X-Linked, Conradi-Hünermann Syndrome, Happle Syndrome
- EBP+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
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