3N6W

Crystal structure of human gamma-butyrobetaine hydroxylase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal structure of human gamma-butyrobetaine hydroxylase.

Tars, K.Rumnieks, J.Zeltins, A.Kazaks, A.Kotelovica, S.Leonciks, A.Sharipo, J.Viksna, A.Kuka, J.Liepinsh, E.Dambrova, M.

(2010) Biochem Biophys Res Commun 398: 634-639

  • DOI: https://doi.org/10.1016/j.bbrc.2010.06.121
  • Primary Citation of Related Structures:  
    3N6W

  • PubMed Abstract: 

    Gamma-butyrobetaine hydroxylase (GBBH) is a 2-ketoglutarate-dependent dioxygenase that catalyzes the biosynthesis of l-carnitine by hydroxylation of gamma-butyrobetaine (GBB). l-carnitine is required for the transport of long-chain fatty acids into mitochondria for generating metabolic energy. The only known synthetic inhibitor of GBBH is mildronate (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), which is a non-hydroxylatable analog of GBB. To aid in the discovery of novel GBBH inhibitors by rational drug design, we have solved the three-dimensional structure of recombinant human GBBH at 2.0A resolution. The GBBH monomer consists of a catalytic double-stranded beta-helix (DBSH) domain, which is found in all 2KG oxygenases, and a smaller N-terminal domain. Extensive interactions between two monomers confirm earlier observations that GBBH is dimeric in its biological state. Although many 2KG oxygenases are multimeric, the dimerization interface of GBBH is very different from that of related enzymes. The N-terminal domain of GBBH has a similar fold to the DUF971 superfamily, which consists of several short bacterial proteins with unknown function. The N-terminal domain has a bound Zn ion, which is coordinated by three cysteines and one histidine. Although several other 2KG oxygenases with known structures have more than one domain, none of them resemble the N-terminal domain of GBBH. The N-terminal domain may facilitate dimer formation, but its precise biological role remains to be discovered. The active site of the catalytic domain of GBBH is similar to that of other 2KG oxygenases, and Fe(II)-binding residues form a conserved His-X-Asp-X(n)-His triad, which is found in all related enzymes.


  • Organizational Affiliation

    Biomedical Research and Study Centre, Ratsupites 1, LV1067, Riga, Latvia. kaspars@biomed.lu.lv


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Gamma-butyrobetaine dioxygenase403Homo 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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 164.8α = 90
b = 164.8β = 90
c = 97.78γ = 120
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
SHELXphasing
SOLOMONphasing
REFMACrefinement
PDB_EXTRACTdata extraction
SHELXDphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations