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PDBsum entry 1gp5

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protein ligands metals links
Oxidoreductase PDB id
1gp5
Jmol
Contents
Protein chain
347 a.a. *
Ligands
AKG
MES ×2
DQH
DH2
Metals
_FE
Waters ×210
* Residue conservation analysis
PDB id:
1gp5
Name: Oxidoreductase
Title: Anthocyanidin synthase from arabidopsis thaliana complexed with trans-dihydroquercetin
Structure: Leucoanthocyanidin dioxygenase. Chain: a. Synonym: anthocyanidin synthase. Engineered: yes
Source: Arabidopsis thaliana. Mouse-ear cress. Organism_taxid: 3702. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.20Å     R-factor:   0.204     R-free:   0.237
Authors: R.C.Wilmouth,J.J.Turnbull,R.W.D.Welford,I.J.Clifton, A.G.Prescott,C.J.Schofield
Key ref:
R.C.Wilmouth et al. (2002). Structure and mechanism of anthocyanidin synthase from Arabidopsis thaliana. Structure, 10, 93. PubMed id: 11796114 DOI: 10.1016/S0969-2126(01)00695-5
Date:
30-Oct-01     Release date:   21-Feb-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q96323  (LDOX_ARATH) -  Leucoanthocyanidin dioxygenase
Seq:
Struc:
356 a.a.
347 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.14.11.19  - Leucocyanidin oxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Anthocyanin Biosynthesis
      Reaction: Leucocyanidin + 2-oxoglutarate + O2 = cis- and trans-dihydroquercetins + succinate + CO2 + H2O
Leucocyanidin
Bound ligand (Het Group name = DQH)
corresponds exactly
+
2-oxoglutarate
Bound ligand (Het Group name = AKG)
corresponds exactly
+ O(2)
= cis- and trans-dihydroquercetins
+ succinate
+ CO(2)
+ H(2)O
      Cofactor: Fe(2+); L-ascorbate
Fe(2+)
L-ascorbate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   7 terms 
  Biochemical function     oxidoreductase activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(01)00695-5 Structure 10:93 (2002)
PubMed id: 11796114  
 
 
Structure and mechanism of anthocyanidin synthase from Arabidopsis thaliana.
R.C.Wilmouth, J.J.Turnbull, R.W.Welford, I.J.Clifton, A.G.Prescott, C.J.Schofield.
 
  ABSTRACT  
 
Flavonoids are common colorants in plants and have long-established biomedicinal properties. Anthocyanidin synthase (ANS), a 2-oxoglutarate iron-dependent oxygenase, catalyzes the penultimate step in the biosynthesis of the anthocyanin class of flavonoids. The crystal structure of ANS reveals a multicomponent active site containing metal, cosubstrate, and two molecules of a substrate analog (dihydroquercetin). An additional structure obtained after 30 min exposure to dioxygen is consistent with the oxidation of the dihydroquercetin to quercetin and the concomitant decarboxylation of 2-oxoglutarate to succinate. Together with in vitro studies, the crystal structures suggest a mechanism for ANS-catalyzed anthocyanidin formation from the natural leucoanthocyanidin substrates involving stereoselective C-3 hydroxylation. The structure of ANS provides a template for the ubiquitous family of plant nonhaem oxygenases for future engineering and inhibition studies.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Reactions Catalyzed by 2OG Oxygenases and Their Involvement in the Flavonoid Biosynthetic Pathway(A) The latter stages of the flavonoid biosynthetic pathway leading to anthocyanins, ANS is the penultimate enzyme (FLS, flavonol synthase; FNS, flavone synthase; F3bOH, flavanone 3-b-hydroxylase; DFR, dihydroflavonol reductase; FGT, UDP-glucose:flavonoid 3-O-glucosyltransferase).(B) A generalized hydroxylation reaction as catalyzed by the 2OG oxygenases.(C) The reaction catalyzed by 1-aminocyclopropane-1-carboxylate oxidase (ACCO).
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 93-0) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21070950 G.Wisedchaisri, D.M.Dranow, T.J.Lie, J.B.Bonanno, Y.Patskovsky, S.A.Ozyurt, J.M.Sauder, S.C.Almo, S.R.Wasserman, S.K.Burley, J.A.Leigh, and T.Gonen (2010).
Structural underpinnings of nitrogen regulation by the prototypical nitrogen-responsive transcriptional factor NrpR.
  Structure, 18, 1512-1521.
PDB code: 3nek
20040577 H.S.Kim, H.L.Kim, K.H.Kim, d.o. .J.Kim, S.J.Lee, J.Y.Yoon, H.J.Yoon, H.Y.Lee, S.B.Park, S.J.Kim, J.Y.Lee, and S.W.Suh (2010).
Crystal structure of Tpa1 from Saccharomyces cerevisiae, a component of the messenger ribonucleoprotein complex.
  Nucleic Acids Res, 38, 2099-2110.
PDB codes: 3kt1 3kt4 3kt7
20228795 J.M.Hagel, and P.J.Facchini (2010).
Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy.
  Nat Chem Biol, 6, 273-275.  
20030585 M.Gargouri, J.Chaudière, C.Manigand, C.Maugé, K.Bathany, J.M.Schmitter, and B.Gallois (2010).
The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers.
  Biol Chem, 391, 219-227.  
20333442 S.C.Lee, d.u. .S.Choi, I.S.Hwang, and B.K.Hwang (2010).
The pepper oxidoreductase CaOXR1 interacts with the transcription factor CaRAV1 and is required for salt and osmotic stress tolerance.
  Plant Mol Biol, 73, 409-424.  
19066943 I.Szankowski, H.Flachowsky, H.Li, H.Halbwirth, D.Treutter, I.Regos, M.V.Hanke, K.Stich, and T.C.Fischer (2009).
Shift in polyphenol profile and sublethal phenotype caused by silencing of anthocyanidin synthase in apple (Malus sp.).
  Planta, 229, 681-692.  
18547395 K.Kai, M.Mizutani, N.Kawamura, R.Yamamoto, M.Tamai, H.Yamaguchi, K.Sakata, and B.Shimizu (2008).
Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana.
  Plant J, 55, 989-999.  
18645237 N.Trabelsi, P.Petit, C.Manigand, B.Langlois d'Estaintot, T.Granier, J.Chaudière, and B.Gallois (2008).
Structural evidence for the inhibition of grape dihydroflavonol 4-reductase by flavonols.
  Acta Crystallogr D Biol Crystallogr, 64, 883-891.
PDB codes: 3bxx 3c1t
18476876 O.Yu, and J.M.Jez (2008).
Nature's assembly line: biosynthesis of simple phenylpropanoids and polyketides.
  Plant J, 54, 750-762.  
17157544 A.M.Reddy, V.S.Reddy, B.E.Scheffler, U.Wienand, and A.R.Reddy (2007).
Novel transgenic rice overexpressing anthocyanidin synthase accumulates a mixture of flavonoids leading to an increased antioxidant potential.
  Metab Eng, 9, 95.  
17135241 K.S.Hewitson, B.M.Liénard, M.A.McDonough, I.J.Clifton, D.Butler, A.S.Soares, N.J.Oldham, L.A.McNeill, and C.J.Schofield (2007).
Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates.
  J Biol Chem, 282, 3293-3301.
PDB codes: 2cgn 2cgo
17967013 M.L.Neidig, C.D.Brown, K.M.Light, D.G.Fujimori, E.M.Nolan, J.C.Price, E.W.Barr, J.M.Bollinger, C.Krebs, C.T.Walsh, and E.I.Solomon (2007).
CD and MCD of CytC3 and taurine dioxygenase: role of the facial triad in alpha-KG-dependent oxygenases.
  J Am Chem Soc, 129, 14224-14231.  
17431691 V.Purpero, and G.R.Moran (2007).
The diverse and pervasive chemistries of the alpha-keto acid dependent enzymes.
  J Biol Inorg Chem, 12, 587-601.  
16482161 B.Yu, W.C.Edstrom, J.Benach, Y.Hamuro, P.C.Weber, B.R.Gibney, and J.F.Hunt (2006).
Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB.
  Nature, 439, 879-884.
PDB codes: 2fd8 2fdf 2fdg 2fdh 2fdi 2fdj 2fdk
16669781 E.Grotewold (2006).
The genetics and biochemistry of floral pigments.
  Annu Rev Plant Biol, 57, 761-780.  
16702218 J.Nakajima, Y.Sato, T.Hoshino, M.Yamazaki, and K.Saito (2006).
Mechanistic study on the oxidation of anthocyanidin synthase by quantum mechanical calculation.
  J Biol Chem, 281, 21387-21398.  
16858410 O.Sundheim, C.B.Vågbø, M.Bjørås, M.M.Sousa, V.Talstad, P.A.Aas, F.Drabløs, H.E.Krokan, J.A.Tainer, and G.Slupphaug (2006).
Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.
  EMBO J, 25, 3389-3397.
PDB code: 2iuw
16731970 T.A.Müller, M.I.Zavodszky, M.Feig, L.A.Kuhn, and R.P.Hausinger (2006).
Structural basis for the enantiospecificities of R- and S-specific phenoxypropionate/alpha-ketoglutarate dioxygenases.
  Protein Sci, 15, 1356-1368.  
16332884 C.L.Wei, Y.B.Yang, C.H.Deng, W.C.Liu, J.S.Hsu, Y.C.Lin, S.H.Liaw, and Y.C.Tsai (2005).
Directed evolution of Streptomyces clavuligerus deacetoxycephalosporin C synthase for enhancement of penicillin G expansion.
  Appl Environ Microbiol, 71, 8873-8880.  
16181493 D.R.Lester, A.Phillips, P.Hedden, and I.Andersson (2005).
Purification and kinetic studies of recombinant gibberellin dioxygenases.
  BMC Plant Biol, 5, 19.  
  16511070 E.Bitto, C.A.Bingman, S.T.Allard, G.E.Wesenberg, D.J.Aceti, R.L.Wrobel, R.O.Frederick, H.Sreenath, F.C.Vojtik, W.B.Jeon, C.S.Newman, J.Primm, M.R.Sussman, B.G.Fox, J.L.Markley, and G.N.Phillips (2005).
The structure at 2.4 A resolution of the protein from gene locus At3g21360, a putative Fe(II)/2-oxoglutarate-dependent enzyme from Arabidopsis thaliana.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 469-472.
PDB code: 1y0z
16186124 M.A.McDonough, K.L.Kavanagh, D.Butler, T.Searls, U.Oppermann, and C.J.Schofield (2005).
Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease.
  J Biol Chem, 280, 41101-41110.
PDB code: 2a1x
16106293 R.W.Welford, I.J.Clifton, J.J.Turnbull, S.C.Wilson, and C.J.Schofield (2005).
Structural and mechanistic studies on anthocyanidin synthase catalysed oxidation of flavanone substrates: the effect of C-2 stereochemistry on product selectivity and mechanism.
  Org Biomol Chem, 3, 3117-3126.
PDB code: 2brt
15856159 S.Kim, R.Jones, K.S.Yoo, and L.M.Pike (2005).
The L locus, one of complementary genes required for anthocyanin production in onions (Allium cepa), encodes anthocyanidin synthase.
  Theor Appl Genet, 111, 120-127.  
15930622 X.Ma, J.Koepke, A.Bayer, G.Fritzsch, H.Michel, and J.Stöckigt (2005).
Crystallization and preliminary X-ray analysis of native and selenomethionyl vinorine synthase from Rauvolfia serpentina.
  Acta Crystallogr D Biol Crystallogr, 61, 694-696.  
15725058 B.S.Winkel (2004).
Metabolic channeling in plants.
  Annu Rev Plant Biol, 55, 85.  
15604673 C.Delessert, I.W.Wilson, D.Van Der Straeten, E.S.Dennis, and R.Dolferus (2004).
Spatial and temporal analysis of the local response to wounding in Arabidopsis leaves.
  Plant Mol Biol, 55, 165-181.  
15122348 C.J.Schofield, and P.J.Ratcliffe (2004).
Oxygen sensing by HIF hydroxylases.
  Nat Rev Mol Cell Biol, 5, 343-354.  
15596008 D.Anzellotti, and R.K.Ibrahim (2004).
Molecular characterization and functional expression of flavonol 6-hydroxylase.
  BMC Plant Biol, 4, 20.  
14570878 J.J.Turnbull, J.Nakajima, R.W.Welford, M.Yamazaki, K.Saito, and C.J.Schofield (2004).
Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis: anthocyanidin synthase, flavonol synthase, and flavanone 3beta-hydroxylase.
  J Biol Chem, 279, 1206-1216.  
15466573 J.S.Hsu, Y.B.Yang, C.H.Deng, C.L.Wei, S.H.Liaw, and Y.C.Tsai (2004).
Family shuffling of expandase genes to enhance substrate specificity for penicillin G.
  Appl Environ Microbiol, 70, 6257-6263.  
14718929 K.Valegård, A.C.Terwisscha van Scheltinga, A.Dubus, G.Ranghino, L.M.Oster, J.Hajdu, and I.Andersson (2004).
The structural basis of cephalosporin formation in a mononuclear ferrous enzyme.
  Nat Struct Mol Biol, 11, 95.
PDB codes: 1unb 1uo9 1uob 1uof 1uog
15489165 Z.Zhang, J.S.Ren, I.J.Clifton, and C.J.Schofield (2004).
Crystal structure and mechanistic implications of 1-aminocyclopropane-1-carboxylic acid oxidase--the ethylene-forming enzyme.
  Chem Biol, 11, 1383-1394.
PDB codes: 1w9y 1wa6
12642663 M.J.Ryle, K.D.Koehntop, A.Liu, L.Que, and R.P.Hausinger (2003).
Interconversion of two oxidized forms of taurine/alpha-ketoglutarate dioxygenase, a non-heme iron hydroxylase: evidence for bicarbonate binding.
  Proc Natl Acad Sci U S A, 100, 3790-3795.  
12814641 M.Mukherji, C.J.Schofield, A.S.Wierzbicki, G.A.Jansen, R.J.Wanders, and M.D.Lloyd (2003).
The chemical biology of branched-chain lipid metabolism.
  Prog Lipid Res, 42, 359-376.  
12517755 R.W.Welford, I.Schlemminger, L.A.McNeill, K.S.Hewitson, and C.J.Schofield (2003).
The selectivity and inhibition of AlkB.
  J Biol Chem, 278, 10157-10161.  
12940955 S.Abrahams, E.Lee, A.R.Walker, G.J.Tanner, P.J.Larkin, and A.R.Ashton (2003).
The Arabidopsis TDS4 gene encodes leucoanthocyanidin dioxygenase (LDOX) and is essential for proanthocyanidin synthesis and vacuole development.
  Plant J, 35, 624-636.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.