3MS5 | pdb_00003ms5

Crystal Structure of Human gamma-butyrobetaine,2-oxoglutarate dioxygenase 1 (BBOX1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 
    0.183 (Depositor), 0.190 (DCC) 
  • R-Value Work: 
    0.147 (Depositor), 0.150 (DCC) 
  • R-Value Observed: 
    0.149 (Depositor) 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural and mechanistic studies on gamma-butyrobetaine hydroxylase.

Leung, I.K.Krojer, T.J.Kochan, G.T.Henry, L.von Delft, F.Claridge, T.D.Oppermann, U.McDonough, M.A.Schofield, C.J.

(2010) Chem Biol 17: 1316-1324

  • DOI: https://doi.org/10.1016/j.chembiol.2010.09.016
  • Primary Citation of Related Structures:  
    3MS5, 3O2G

  • PubMed Abstract: 

    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.


  • Organizational Affiliation
    • The Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX13TA, UK.

Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Gamma-butyrobetaine dioxygenase388Homo sapiensMutation(s): 0 
Gene Names: BBHBBOXBBOX1
EC: 1.14.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O75936 (Homo sapiens)
Explore O75936 
Go to UniProtKB:  O75936
PHAROS:  O75936
GTEx:  ENSG00000129151 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75936
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
REE
Query on REE

Download Ideal Coordinates CCD File 
E [auth A]2-(2-carboxyethyl)-1,1,1-trimethyldiazanium
C6 H15 N2 O2
PVBQYTCFVWZSJK-UHFFFAOYSA-O
OGA
Query on OGA

Download Ideal Coordinates CCD File 
D [auth A]N-OXALYLGLYCINE
C4 H5 N O5
BIMZLRFONYSTPT-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
NI
Query on NI

Download Ideal Coordinates CCD File 
B [auth A]NICKEL (II) ION
Ni
VEQPNABPJHWNSG-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free:  0.183 (Depositor), 0.190 (DCC) 
  • R-Value Work:  0.147 (Depositor), 0.150 (DCC) 
  • R-Value Observed: 0.149 (Depositor) 
Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.366α = 90
b = 107.366β = 90
c = 205.054γ = 120
Software Package:
Software NamePurpose
MAR345data collection
SHARPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2010-05-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2019-03-20
    Changes: Data collection, Database references
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations