2XFL

Induced-fit and allosteric effects upon polyene binding revealed by crystal structures of the Dynemicin thioesterase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.199 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Induced-Fit Upon Ligand Binding Revealed by Crystal Structures of the Hot-Dog Fold Thioesterase in Dynemicin Biosynthesis.

Liew, C.W.Sharff, A.Kotaka, M.Kong, R.Sun, H.Qureshi, I.Bricogne, G.Liang, Z.Lescar, J.

(2010) J Mol Biol 404: 291

  • DOI: https://doi.org/10.1016/j.jmb.2010.09.041
  • Primary Citation of Related Structures:  
    2XEM, 2XFL

  • PubMed Abstract: 

    Dynemicins are structurally related 10-membered enediyne natural products isolated from Micromonospora chernisa with potent antitumor and antibiotic activity. The early biosynthetic steps of the enediyne moiety of dynemicins are catalyzed by an iterative polyketide synthase (DynE8) and a thioesterase (DynE7). Recent studies indicate that the function of DynE7 is to off-load the linear biosynthetic intermediate assembled on DynE8. Here, we report crystal structures of DynE7 in its free form at 2.7 Å resolution and of DynE7 in complex with the DynE8-produced all-trans pentadecen-2-one at 2.1 Å resolution. These crystal structures reveal that upon ligand binding, significant conformational changes throughout the substrate-binding tunnel result in an expanded tunnel that traverses an entire monomer of the tetrameric DynE7 protein. The enlarged inner segment of the channel binds the carbonyl-conjugated polyene mainly through hydrophobic interactions, whereas the putative catalytic residues are located in the outer segment of the channel. The crystallographic information reinforces an unusual catalytic mechanism that involves a strictly conserved arginine residue for this subfamily of hot-dog fold thioesterases, distinct from the typical mechanism for hot-dog fold thioesterases that utilizes an acidic residue for catalysis.


  • Organizational Affiliation

    School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DYNE7
A, B, C, D, E
A, B, C, D, E, F, G, H
142Micromonospora chersinaMutation(s): 0 
UniProt
Find proteins for Q84HI7 (Micromonospora chersina)
Explore Q84HI7 
Go to UniProtKB:  Q84HI7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ84HI7
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.199 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.11α = 90
b = 179.127β = 111.25
c = 64.177γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-10-13
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Other, Refinement description