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Emopamil binding protein
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| 3-beta-hydroxysteroid-Δ8,Δ7-isomerase | |||||||||
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| Identifiers | |||||||||
| EC no. | 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.[5] 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.[6] 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.[7]
Function
[edit]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.[8] In the Bloch pathway of cholesterol biosynthesis, EBP converts zymosterol to dehydrolathosterol, while in the Kandutsch–Russell pathway it converts zymostenol to lathosterol.
Clinical significance
[edit]Mutations in EBP cause Conradi–Hünermann syndrome and impairs cholesterol biosynthesis.[9] 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.[10]
Research areas
[edit]Remyelination and MS
[edit]The inhibition of EBP promotes oligodendrocyte formation, which may help remyelination and thus limit multiple sclerosis development. [11]
Cloning
[edit]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.[7]
See also
[edit]References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000147155 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031168 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Guggenberger C, Ilgen D, Adamski J (May 2007). "Functional analysis of cholesterol biosynthesis by RNA interference". The Journal of Steroid Biochemistry and Molecular Biology. 104 (3–5): 105–109. doi:10.1016/j.jsbmb.2007.03.001. PMID 17498944. S2CID 20838858.
- ^ Moebius FF, Hanner M, Knaus HG, 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.
- ^ a b Hanner M, Moebius FF, Weber F, Grabner M, Striessnig J, Glossmann H (March 1995). "Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression". The Journal of Biological Chemistry. 270 (13): 7551–7557. doi:10.1074/jbc.270.13.7551. PMID 7706302.
- ^ Silve S, Dupuy PH, Labit-Lebouteiller C, Kaghad M, Chalon P, Rahier A, 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.
- ^ Barboza-Cerda MC, Wong LJ, Martínez-de-Villarreal LE, Zhang VW, Déctor MA (July 2014). "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. doi:10.1002/ajmg.a.36508. PMID 24700572. S2CID 6501291.
- ^ Krakow D (2018). "Chondrodysplasia Punctata". In Copel JA, D'Alton ME, Reapply WC, Feltovich H, Gratacós E, Krakow D, Odibo AO, Platt LD, Tutschek B (eds.). Obstetric Imaging: Fetal Diagnosis and Care (2nd ed.). Elsevier. pp. 259–261. doi:10.1016/b978-0-323-44548-1.00048-6. ISBN 978-0-323-44548-1.
- ^ Dorel R, Sun D, Carruthers N, Castanedo GM, Ung PM, Factor DC, et al. (March 2024). "Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation". Journal of Medicinal Chemistry. 67 (6): 4819–4832. doi:10.1021/acs.jmedchem.3c02396. PMID 38470227.
External links
[edit]- GeneReviews/NCBI/NIH/UW entry on Chondrodysplasia Punctata 2, X-Linked, Conradi-Hünermann Syndrome, Happle Syndrome
- EBP+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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