3TVQ

Crystal structure of TCM Aro/Cyc complexed with trans-dihidroquercetin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.67 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Insight into the Molecular Basis of Aromatic Polyketide Cyclization: Crystal Structure and in Vitro Characterization of WhiE-ORFVI.

Lee, M.Y.Ames, B.D.Tsai, S.C.

(2012) Biochemistry 51: 3079-3091

  • DOI: https://doi.org/10.1021/bi201705q
  • Primary Citation of Related Structures:  
    3TL1, 3TVQ, 3TVR

  • PubMed Abstract: 

    Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled polyketide chain catalyzed by aromatase/cyclase (ARO/CYC), which serves as a key control point in aromatic ring formation. How different ARO/CYCs promote different cyclization patterns is not well understood. The whiE locus of Streptomyces coelicolor A3(2) is responsible for the biosynthesis of an aromatic polyketide precursor to the gray spore pigment. The WhiE ARO/CYC catalyzes the regiospecific C9-C14 and C7-C16 cyclization and aromatization of a 24-carbon polyketide chain. WhiE ARO/CYC shares a high degree of similarity to another nonreducing PKS ARO/CYC, TcmN ARO/CYC. This paper presents the apo crystal structure of WhiE ARO/CYC, and cocrystal structures of WhiE and TcmN ARO/CYCs bound with polycyclic aromatic compounds that mimic the respective ARO/CYC products. Site-directed mutagenesis coupled with in vitro PKS reconstitution assays was used to characterize the interior pocket residues of WhiE ARO/CYC. The results confirmed that the interior pocket of ARO/CYCs is a critical determinant of polyketide cyclization specificity. A unified ARO/CYC-mediated cyclization mechanism is proposed on the basis of these structural and functional results.


  • Organizational Affiliation

    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Multifunctional cyclase-dehydratase-3-O-methyl transferase tcmN169Streptomyces glaucescensMutation(s): 0 
Gene Names: tcmN
UniProt
Find proteins for P16559 (Streptomyces glaucescens)
Explore P16559 
Go to UniProtKB:  P16559
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16559
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DQH
Query on DQH

Download Ideal Coordinates CCD File 
B [auth A](2R,3R)-2-(3,4-DIHYDROXYPHENYL)-3,5,7-TRIHYDROXY-2,3-DIHYDRO-4H-CHROMEN-4-ONE
C15 H12 O7
CXQWRCVTCMQVQX-LSDHHAIUSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.67 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.455α = 90
b = 105.011β = 90
c = 51.088γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-04
    Type: Initial release
  • Version 1.1: 2012-04-25
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description