2-Oxoglutarate dependent

Turnbull JJ, Nakajima J, Welford RW, Yamazaki M, Saito K and Schofield CJ. 2004. Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis anthocyanidin synthase, flavonol synthase, and flavanone 33-hydroxylase. J Biol Chem 279 1206-1216. 

Scheme 3. Reaction of 2-oxoglutarate dependent iron enzymes (8).

Scheme 4. Mechanism of the 2-oxoglutarate dependent iron oxygenases (8).

Prolyl 4-hydroxylation is the most abundant posttranslational modification of collagens. 4-Hydroxylation of proline residues increases the stability of the triple helix and is a key element in the folding of the collagen triple helix. " In vertebrates, almost all the Yaa position prolines of the Gly-Xaa-Yaa repeat are modified to 4(I( )-hydroxylproline by the enzyme P4H (EC 1.14.11.2), a member of Fe(II)- and 2-oxoglutarate-dependent dioxygenases. This enzyme is an 0 2/ b2-type heterotetramer in which the / subunit is PDI (EC 5.3.4.1), which is a ubiquitous disulfide bond catalyst. The P4H a subunit needs the 13 subunit for solubility however, the 13 subunit, PDI, is soluble by itself and is present in excess in the ER. Three isoforms of the a subunit have been identified and shown to combine with PDI to form [a(I)]2/ 2) [< (II)]2/32> or [a(III)]2/32 tetramers, called the type... 

Fig. 6.2 The flavonoid core biosynthetic pathway. The P450s and 2-oxoglutarate-dependent dioxygenases (2-ODDs) are indicated by underlined and bolded titles, respectively. F3 H and F3 5 H are capable of using flavanones (2-3 = single bond, R1 = H), flavones (2-3 = double bond, R1 = H), dihydroflavonols (2-3 = single bond, R1 = OH), or flavonols (2-3 = double bond, R1 = OH) for a substrate. FNS activity has been indicated with two different enzymes, FNS-11 (P450) and the less-common FNS-I (2-ODD)...

Flavone synthase (FNS EC 1.14.11.22) introduces a double bond between C2 and C3 of a flavanone to produce the corresponding flavone. This activity was initially identified in parsley cell suspension cultures and subsequently shown to be encoded by a 2-oxoglutarate-dependent dioxygenase [67, 78, 79], This enzyme, now known as FNS-I, appears to have very limited distribution. To date, it has only been identified in the Apiaceae family (Umbellifers). The more widely occurring FNS-II (CYP93B) was initially identified from snapdragon (Antirrhinum majus) flowers [80] and was subsequently shown to be a P450 enzyme. FNS-I, FNS-II, and the various roles flavones play in plant species have recently been reviewed by Martens and Mithofer [81], Subsequent to this review, Yu et al. [82] demonstrated that the characteristic lack of natural accumulation of flavones in Brassicaceae could not be overcome in A. thaliana even by overexpression of recombinant parsley FNS-I. 

Halbwirth H, Fischer TC, Schlangen K, Rademacher W, Schleifer K, Forkmann G, Stitch K (2006) Screening for inhibitors of 2-oxoglutarate-dependent dioxygenases flavanone 3-hydroxylase and flavonol synthase. Plant Sd 171 194-205... 

Saito K, Kobayashi M, Gong Z, Tanaka Y, Yamazaki M (1999) Direct evidence for anthocyanidin synthase as a 2-oxoglutarate-dependent oxygenase molecular cloning and functional expression of cDNA from a red form of Perilla frutescens. Plant J 17(2) 181-189... 

Martens S, Forkmann G, Britsch L, WeUmann F, Matem U, Lukacin R (2003) Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley. FEBS Lett 544 (l-3) 93-98... 

Matsuda, J. et al.. Molecular cloning of hyoscyamine 6p-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, from cultured roots of Hyoscyamus niger. J. Biol Chem., 266, 9460, 1991. 

Britsch, L., Purification and characterization of flavone synthase 1, a 2-oxoglutarate-dependent desaturase. Arch. Biochem. Biophys., 282, 152, 1990. 

Anzelotti, D. and Ibrahim, R.K., Novel flavonol 2-oxoglutarate dependent dioxygenase affinity purification, characterization, and kinetic properties. Arch. Biochem. Biophys., 382, 161, 2000. 

Roemmelt, S. et al., Formation of novel flavonoids in apple (Malus x domesticd) treated with the 2-oxoglutarate-dependent dioxygenase inhibitor prohexadione-Ca, Phytochemistry, 64, 709, 2003. 

Formation of the 3-hydroxymyristoyl groups of lipid A (Fig. 8-30) requires 02. Comparisons of amino acid sequences suggest that an Fe2+/ 2-oxoglutarate-dependent oxygenase is involved.358 Write a balanced equation for this reaction. 

In the synthesis of anthocyanidins (Box 21-E) another Fe2+/2-oxoglutarate-dependent oxygenase acts on the colorless leukoanthrocyanidin, which is then converted to the colored anthocyanidin ... 

The vitamins K and other naphthoquinones arise from O-succinylbenzoate84 86 whose synthesis from chorismate and 2-oxoglutarate depends upon a thiamine diphosphate-bound intermediate, as indicated in Fig. 25-4. Elimination of pyruvate yields O-succinylbenzoate. The remaining reactions of decarboxylation, methylation, and prenylation (Fig. 25-4) resemble those of ubiquinone synthesis. 

In plants accumulating anthocyanins, flavonols, and proanthocyanidins, naringenin is stereospecifically hydroxylated at position 3 of the C-ring (C3) by the 2-oxoglutarate-dependent dioxygenase flavanone 3-hydroxylase (F3H, EC 1.14.11.9) to yield the 3-hydroxy-trans-flavanone (syn. dihydroflavonol) dihy-drokaempferol [Springob et al., 2003] (Fig.21 2). Dihydroquercetin (3, 4, 5,5, 7-... 

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