Rabphilin

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	== Function ==		== Function ==
-	'''Rabphilin''' or '''berberine bridge-forming enzyme''' (RO) is part of the alkaloids biosynthesis pathway catalyzing the conversion of (S)-reticuline to (S)-scoulerine<ref>PMID:1946465</ref>. RO catalyzes the cyclization of the N-methyl moiety of (S)-reticuline into the berberine bridge carbon, C-8 of (S)- <ref>PMID:7592663</ref>.	+	'''Rabphilin''' (Rab) is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites<ref>PMID:26679993</ref>.
	== Relevance ==		== Relevance ==
-	Reticuline is a precursor of morphine and has potent central nervous system depressing effects<ref>PMID:9720612</ref>.	+	Rab is a major auto antigen in lymphocytic infundibulo-neurohypophysitis (LINH). Antibodies to Rab may serve as a biomarker for the diagnosis of LINH<ref>PMID:25919460</ref>.
	== Structural highlights ==		== Structural highlights ==

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Revision as of 09:29, 4 February 2021

spinqualitylabelsall models Structure of glycosylated California poppy reticuline oxidase complex with reticuline and FAD (PDB code 5lob) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Rabphilin (Rab) is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites[1]. Relevance Rab is a major auto antigen in lymphocytic infundibulo-neurohypophysitis (LINH). Antibodies to Rab may serve as a biomarker for the diagnosis of LINH[2]. Structural highlights The 3D structure of the complex between RO and its substrate reticuline show the cofactor FAD having bicovalent attachment to RO His and Cys. The substrate reticuline is seen in the active site cavity interacting with FAD and numerous RO sidechains[3].

3D Structures of rabphilin 3-A

Updated on 04-February-2021

Domains: C2A 378-510; C2B 541-680

2cm5, 2cm6 – rRab C2B domain – rat
4izk – rRab C2B domain - NMR
5lo8 – rRab C2B domain + inositol phosphate derivative
5lob, 5low – rRab C2B domain + SNAP25
2chd, 4lt7 – rRab C2A domain
4np9, 4ns0 – rRab C2A domain + inositol phosphate derivative
1zbd – rRab 19-217 (mutant) + rRab effector domain 40-179 (mutant) + GTP
2k3h – mRab C2A domain - mouse - NMR

References

1. ↑ Stanic J, Carta M, Eberini I, Pelucchi S, Marcello E, Genazzani AA, Racca C, Mulle C, Di Luca M, Gardoni F. Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex. Nat Commun. 2015 Dec 18;6:10181. doi: 10.1038/ncomms10181. PMID:26679993 doi:http://dx.doi.org/10.1038/ncomms10181
2. ↑ Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y. Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. J Clin Endocrinol Metab. 2015 Jul;100(7):E946-54. doi: 10.1210/jc.2014-4209. Epub, 2015 Apr 28. PMID:25919460 doi:http://dx.doi.org/10.1210/jc.2014-4209
3. ↑ Winkler A, Lyskowski A, Riedl S, Puhl M, Kutchan TM, Macheroux P, Gruber K. A concerted mechanism for berberine bridge enzyme. Nat Chem Biol. 2008 Dec;4(12):739-41. Epub 2008 Oct 26. PMID:18953357 doi:http://dx.doi.org/10.1038/nchembio.123