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| [[2cm5]], [[2cm6]] – rRab C2B domain 541-680 – rat<br /> | | [[2cm5]], [[2cm6]] – rRab C2B domain 541-680 – rat<br /> |
| [[3rbp]] – rRab C2B domain - NMR<br /> | | [[4izk]] – rRab C2B domain - NMR<br /> |
| [[5lo8]] – rRab C2B domain + inositol phosphate derivative<br /> | | [[5lo8]] – rRab C2B domain + inositol phosphate derivative<br /> |
| [[5lob]], [[5low]] – rRab C2AB domain + SNAP25<br /> | | [[5lob]], [[5low]] – rRab C2AB domain + SNAP25<br /> |
Revision as of 13:38, 3 February 2021
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Function
Rabphilin or berberine bridge-forming enzyme (RO) is part of the alkaloids biosynthesis pathway catalyzing the conversion of (S)-reticuline to (S)-scoulerine[1]. RO catalyzes the cyclization of the N-methyl moiety of (S)-reticuline into the berberine bridge carbon, C-8 of (S)- [2].
Relevance
Reticuline is a precursor of morphine and has potent central nervous system depressing effects[3].
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[4].
- ↑ Dittrich H, Kutchan TM. Molecular cloning, expression, and induction of berberine bridge enzyme, an enzyme essential to the formation of benzophenanthridine alkaloids in the response of plants to pathogenic attack. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9969-73. PMID:1946465
- ↑ Kutchan TM, Dittrich H. Characterization and mechanism of the berberine bridge enzyme, a covalently flavinylated oxidase of benzophenanthridine alkaloid biosynthesis in plants. J Biol Chem. 1995 Oct 13;270(41):24475-81. doi: 10.1074/jbc.270.41.24475. PMID:7592663 doi:https://dx.doi.org/10.1074/jbc.270.41.24475
- ↑ Morais LC, Barbosa-Filho JM, Almeida RN. Central depressant effects of reticuline extracted from Ocotea duckei in rats and mice. J Ethnopharmacol. 1998 Aug;62(1):57-61. doi: 10.1016/s0378-8741(98)00044-0. PMID:9720612 doi:https://dx.doi.org/10.1016/s0378-8741(98)00044-0
- ↑ 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:https://dx.doi.org/10.1038/nchembio.123
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3D Structures of rabphilin 3-A
Updated on 03-February-2021
2cm5, 2cm6 – rRab C2B domain 541-680 – rat
4izk – rRab C2B domain - NMR
5lo8 – rRab C2B domain + inositol phosphate derivative
5lob, 5low – rRab C2AB domain + SNAP25
2chd, 4lt7 – rRab C2A domain 378-510
4np9, 4ns0 – rRab C2A domain + inositol phosphate derivative
1zbd – rRab 19-217 (mutant) + rRab effector domain 40-179 (mutant) + GTP
2k3h – mRab C2A domain 378-510 - mouse - NMR
References
