4I4J

The structure of SgcE10, the ACP-polyene thioesterase involved in C-1027 biosynthesis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.78 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis.

Annaval, T.Rudolf, J.D.Chang, C.Y.Lohman, J.R.Kim, Y.Bigelow, L.Jedrzejczak, R.Babnigg, G.Joachimiak, A.Phillips Jr., G.N.Shen, B.

(2017) ACS Omega 2: 5159-5169

  • DOI: https://doi.org/10.1021/acsomega.7b00933
  • Primary Citation of Related Structures:  
    4I4J

  • PubMed Abstract: 

    Enediynes are potent natural product anticancer antibiotics, and are classified as 9- or 10-membered according to the size of their enediyne core carbon skeleton. Both 9- and 10-membered enediyne cores are biosynthesized by the enediyne polyketide synthase (PKSE), thioesterase (TE), and PKSE-associated enzymes. Although the divergence between 9- and 10-membered enediyne core biosynthesis remains unclear, it has been observed that nascent polyketide intermediates, tethered to the acyl carrier protein (ACP) domain of PKSE, could be released by TE in the absence of the PKSE-associated enzymes. In this study, we determined the crystal structure of SgcE10, the TE that participates in the biosynthesis of the 9-membered enediyne C-1027. Structural comparison of SgcE10 with CalE7 and DynE7, two TEs that participate in the biosynthesis of the 10-membered enediynes calicheamicin and dynemicin, respectively, revealed that they share a common α/β hot-dog fold. The amino acids involved in both substrate binding and catalysis are conserved among SgcE10, CalE7, and DynE7. The volume and the shape of the substrate-binding channel and active site in SgcE10, CalE7, and DynE7 confirm that TEs from both 9- and 10-membered enediyne biosynthetic machineries bind the linear form of similar ACP-tethered polyene intermediates. Taken together, these findings further support the proposal that the divergence between 9- and 10-membered enediyne core biosynthesis occurs beyond PKSE and TE catalysis.


  • Organizational Affiliation

    Department of Chemistry, Department of Molecular Medicine, and Natural Products Library Initiative at The Scripps Research Institute, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ACP-polyene thioesterase
A, B, C, D, E
A, B, C, D, E, F, G, H
159Streptomyces globisporusMutation(s): 0 
UniProt
Find proteins for Q8GME8 (Streptomyces globisporus)
Explore Q8GME8 
Go to UniProtKB:  Q8GME8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8GME8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.416α = 90
b = 184.526β = 95.6
c = 59.401γ = 90
Software Package:
Software NamePurpose
SBC-Collectdata collection
HKL-3000data collection
HKL-3000phasing
PHENIXmodel building
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-12-12
    Type: Initial release
  • Version 1.1: 2012-12-19
    Changes: Structure summary
  • Version 1.2: 2022-05-04
    Changes: Database references, Derived calculations