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PDBsum entry 3o2g
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Oxidoreductase
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PDB id
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3o2g
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Contents |
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* Residue conservation analysis
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PDB id:
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Oxidoreductase
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Title:
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Crystal structure of human gamma-butyrobetaine,2-oxoglutarate dioxygenase 1 (bbox1)
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Structure:
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Gamma-butyrobetaine dioxygenase. Chain: a. Synonym: gamma-butyrobetaine,2-oxoglutarate dioxygenase, gamma- butyrobetaine hydroxylase, gamma-bbh. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: bbox1, bbh, bbox. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
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Resolution:
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1.78Å
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R-factor:
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0.149
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R-free:
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0.176
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Authors:
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T.Krojer,G.Kochan,M.A.Mcdonough,F.Von Delft,I.K.H.Leung,L.Henry, T.D.W.Claridge,E.Pilka,E.Ugochukwu,J.Muniz,P.Filippakopoulos, C.Bountra,C.H.Arrowsmith,J.Weigelt,A.Edwards,K.L.Kavanagh, C.J.Schofield,U.Oppermann,Structural Genomics Consortium (Sgc)
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Key ref:
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I.K.Leung
et al.
(2010).
Structural and mechanistic studies on γ-butyrobetaine hydroxylase.
Chem Biol,
17,
1316-1324.
PubMed id:
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Date:
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22-Jul-10
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Release date:
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15-Sep-10
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PROCHECK
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Headers
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References
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O75936
(BODG_HUMAN) -
Gamma-butyrobetaine dioxygenase from Homo sapiens
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Seq:
Struc:
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387 a.a.
386 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.1.14.11.1
- gamma-butyrobetaine dioxygenase.
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Reaction:
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4-(trimethylamino)butanoate + 2-oxoglutarate + O2 = carnitine + succinate + CO2
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4-(trimethylamino)butanoate
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+
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2-oxoglutarate
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+
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O2
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=
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carnitine
Bound ligand (Het Group name = )
matches with 90.91% similarity
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+
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succinate
Bound ligand (Het Group name = )
matches with 40.00% similarity
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+
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CO2
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Cofactor:
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Fe(2+); L-ascorbate
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Fe(2+)
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L-ascorbate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Chem Biol
17:1316-1324
(2010)
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PubMed id:
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Structural and mechanistic studies on γ-butyrobetaine hydroxylase.
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I.K.Leung,
T.J.Krojer,
G.T.Kochan,
L.Henry,
F.von Delft,
T.D.Claridge,
U.Oppermann,
M.A.McDonough,
C.J.Schofield.
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ABSTRACT
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The final step in carnitine biosynthesis is catalyzed by γ-butyrobetaine (γBB)
hydroxylase (BBOX), an iron/2-oxoglutarate (2OG) dependent oxygenase. BBOX is
inhibited by trimethylhydrazine-propionate (THP), a clinically used compound. We
report structural and mechanistic studies on BBOX and its reaction with THP.
Crystallographic and sequence analyses reveal that BBOX and trimethyllysine
hydroxylase form a subfamily of 2OG oxygenases that dimerize using an N-terminal
domain. The crystal structure reveals the active site is enclosed and how THP
competes with γBB. THP is a substrate giving formaldehyde (supporting
structural links with histone demethylases), dimethylamine, malonic acid
semi-aldehyde, and an unexpected product with an additional carbon-carbon bond
resulting from N-demethylation coupled to oxidative rearrangement, likely via an
unusual radical mechanism. The results provide a basis for development of
improved BBOX inhibitors and may inspire the discovery of additional
rearrangement reactions.
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Links
