2brt

File:2brt.gif

spinqualitylabelsall models 2brt, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ANTHOCYANIDIN SYNTHASE FROM ARABIDOPSIS THALIANA COMPLEXED WITH NARINGENIN

OverviewOverview

During the biosynthesis of the tricyclic flavonoid natural products in, plants, oxidative modifications to the central C-ring are catalysed by, Fe(ii) and 2-oxoglutarate dependent oxygenases. The reactions catalysed by, three of these enzymes; flavone synthase I, flavonol synthase and, anthocyanidin synthase (ANS), are formally desaturations. In comparison, flavanone 3beta-hydroxylase catalyses hydroxylation at the C-3 pro-R, position of 2S-naringenin. Incubation of ANS with the unnatural substrate, (+/-)-naringenin results in predominantly C-3 hydroxylation to give, cis-dihydrokaempferol as the major product; trans-dihydrokaempferol and, the desaturation product, apigenin are also observed. Labelling studies, have demonstrated that some of the formal desaturation reactions catalysed, by ANS proceed via initial C-3 hydroxylation followed by dehydration at, the active site. We describe analyses of the reaction of ANS with 2S- and, 2R-naringenin substrates, including the anaerobic crystal structure of an, ANS-Fe-2-oxoglutarate-naringenin complex. Together the results reveal that, for the 'natural' C-2 stereochemistry of 2S-naringenin, C-3 hydroxylation, predominates (>9 : 1) over desaturation, probably due to the, inaccessibility of the C-2 hydrogen to the iron centre. For the, 2R-naringenin substrate, desaturation is significantly increased relative, to C-3 hydroxylation (ca. 1 : 1); this is probably a result of both the, C-3 pro-S and C-2 hydrogen atoms being accessible to the reactive, oxidising intermediate in this substrate. In contrast to the, hydroxylation-elimination desaturation mechanism for some ANS substrates, the results imply that the ANS catalysed desaturation of 2R-naringenin to, form apigenin proceeds with a syn-arrangement of eliminated hydrogen atoms, and not via an oxygenated (gem-diol) flavonoid intermediate. Thus, by, utilising flavonoid substrates with different C-2 stereochemistries, the, balance between C-3 hydroxylation or C-2, C-3 desaturation mechanisms can, be altered.

About this StructureAbout this Structure

2BRT is a Single protein structure of sequence from Arabidopsis thaliana with FE2, AKG and NAR as ligands. Active as Leucocyanidin oxygenase, with EC number 1.14.11.19 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Structural and mechanistic studies on anthocyanidin synthase catalysed oxidation of flavanone substrates: the effect of C-2 stereochemistry on product selectivity and mechanism., Welford RW, Clifton IJ, Turnbull JJ, Wilson SC, Schofield CJ, Org Biomol Chem. 2005 Sep 7;3(17):3117-26. Epub 2005 Aug 1. PMID:16106293

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