4OO2

Streptomyces globisporus C-1027 FAD dependent (S)-3-chloro-β-tyrosine-S-SgcC2 C-5 hydroxylase SgcC apo form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.63 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier Protein-Tethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus.

Chang, C.Y.Lohman, J.R.Cao, H.Tan, K.Rudolf, J.D.Ma, M.Xu, W.Bingman, C.A.Yennamalli, R.M.Bigelow, L.Babnigg, G.Yan, X.Joachimiak, A.Phillips, G.N.Shen, B.

(2016) Biochemistry 55: 5142-5154

  • DOI: https://doi.org/10.1021/acs.biochem.6b00713
  • Primary Citation of Related Structures:  
    4HX6, 4OO2, 4R82

  • PubMed Abstract: 

    C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two-component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-β-tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate. To address the molecular details of substrate specificity, we determined the crystal structures of SgcE6 and SgcC at 1.66 and 2.63 Å resolution, respectively. SgcE6 shares a similar β-barrel fold with the class I HpaC-like flavin reductases. A flexible loop near the active site of SgcE6 plays a role in FAD binding, likely by providing sufficient space to accommodate the AMP moiety of FAD, when compared to that of FMN-utilizing homologues. SgcC shows structural similarity to a few other known FADH2-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. The crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate.


  • Organizational Affiliation

    Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chlorophenol-4-monooxygenase
A, B, C, D
527Streptomyces globisporusMutation(s): 0 
UniProt
Find proteins for Q8GMG6 (Streptomyces globisporus)
Explore Q8GMG6 
Go to UniProtKB:  Q8GMG6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8GMG6
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B, C, D
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.63 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.156α = 90
b = 173.729β = 90
c = 113.859γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
JBluIce-EPICSdata collection
XDSdata reduction
XDSdata scaling
PHASERphasing
PHENIXrefinement

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-12
    Type: Initial release
  • Version 1.1: 2014-02-26
    Changes: Structure summary
  • Version 1.2: 2016-11-16
    Changes: Database references
  • Version 1.3: 2016-12-07
    Changes: Structure summary
  • Version 1.4: 2017-11-22
    Changes: Refinement description
  • Version 1.5: 2023-03-22
    Changes: Database references, Derived calculations, Structure summary