6DAX

X-ray crystal structure of VioC bound to Fe(II), L-homoarginine, and 2-oxoglutarate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.216 

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This is version 1.3 of the entry. See complete history


Literature

Two Distinct Mechanisms for C-C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of alpha-Heteroatom Assistance.

Dunham, N.P.Chang, W.C.Mitchell, A.J.Martinie, R.J.Zhang, B.Bergman, J.A.Rajakovich, L.J.Wang, B.Silakov, A.Krebs, C.Boal, A.K.Bollinger, J.M.

(2018) J Am Chem Soc 140: 7116-7126

  • DOI: https://doi.org/10.1021/jacs.8b01933
  • Primary Citation of Related Structures:  
    6DAW, 6DAX, 6DAZ, 6DB2

  • PubMed Abstract: 

    Hydroxylation of aliphatic carbons by nonheme Fe(IV)-oxo (ferryl) complexes proceeds by hydrogen-atom (H•) transfer (HAT) to the ferryl and subsequent coupling between the carbon radical and Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H•-abstracting ferryl complexes for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C-C desaturations, it has been proposed that a second HAT to the Fe(III)-OH complex from the carbon α to the radical preempts rebound. Deuterium ( 2 H) at the second site should slow this step, potentially making rebound competitive. Desaturations mediated by two related l-arginine-modifying iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases behave oppositely in this key test, implicating different mechanisms. NapI, the l-Arg 4,5-desaturase from the naphthyridinomycin biosynthetic pathway, abstracts H• first from C5 but hydroxylates this site (leading to guanidine release) to the same modest extent whether C4 harbors 1 H or 2 H. By contrast, an unexpected 3,4-desaturation of l-homoarginine (l-hArg) by VioC, the l-Arg 3-hydroxylase from the viomycin biosynthetic pathway, is markedly disfavored relative to C4 hydroxylation when C3 (the second hydrogen donor) harbors 2 H. Anchimeric assistance by N6 permits removal of the C4-H as a proton in the NapI reaction, but, with no such assistance possible in the VioC desaturation, a second HAT step (from C3) is required. The close proximity (≤3.5 Å) of both l-hArg carbons to the oxygen ligand in an X-ray crystal structure of VioC harboring a vanadium-based ferryl mimic supports and rationalizes the sequential-HAT mechanism. The results suggest that, although the sequential-HAT mechanism is feasible, its geometric requirements may make competing hydroxylation unavoidable, thus explaining the presence of α-heteroatoms in nearly all native substrates for Fe/2OG desaturases.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-ketoglutarate-dependent L-arginine hydroxylase338Streptomyces vinaceusMutation(s): 0 
EC: 1.14.11.41
UniProt
Find proteins for Q6WZB0 (Streptomyces vinaceus)
Explore Q6WZB0 
Go to UniProtKB:  Q6WZB0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6WZB0
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.216 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.376α = 90
b = 67.076β = 108.72
c = 62.646γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM119707

Revision History  (Full details and data files)

  • Version 1.0: 2018-05-16
    Type: Initial release
  • Version 1.1: 2018-06-20
    Changes: Data collection, Database references
  • Version 1.2: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references