Reticuline oxidase

Function

Reticuline oxidase 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 .

. Water molecules are shown as red spheres. The ^[4].

.
.

Structure of glycosylated California poppy reticuline oxidase complex with reticuline and FAD (PDB code 3d2d)

Drag the structure with the mouse to rotate

3D Structures of Reticuline oxidase3D Structures of Reticuline oxidase

Updated on 02-February-2021

3d2h, 3d2j – CpRO + FAD – California poppy
3fw7, 3fw8, 4pzf – CpRO (mutant) + FAD
3d2d – CpRO + FAD + reticuline
3fwa, 4ec3 – CpRO (mutant) + FAD + reticuline
3fw9, 3gsy – CpRO + FAD + scoulerine derivative
3d2h – CpRO + FAD + ADP derivative

ReferencesReferences

↑ 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:http://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:http://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:http://dx.doi.org/10.1038/nchembio.123

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] 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

[2] 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:http://dx.doi.org/10.1074/jbc.270.41.24475

[3] 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:http://dx.doi.org/10.1016/s0378-8741(98)00044-0

[4] 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

[1]

[2]

[3]

[4]