1X7G

Actinorhodin Polyketide Ketoreductase, act KR, with NADP bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.211 

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This is version 1.3 of the entry. See complete history


Literature

Structural analysis of actinorhodin polyketide ketoreductase: cofactor binding and substrate specificity

Korman, T.P.Hill, J.A.Vu, T.N.Tsai, S.C.

(2004) Biochemistry 43: 14529-14538

  • DOI: https://doi.org/10.1021/bi048133a
  • Primary Citation of Related Structures:  
    1X7G, 1X7H, 1XR3

  • PubMed Abstract: 

    Aromatic polyketides are a class of natural products that include many pharmaceutically important aromatic compounds. Understanding the structure and function of PKS will provide clues to the molecular basis of polyketide biosynthesis specificity. Polyketide chain reduction by ketoreductase (KR) provides regio- and stereochemical diversity. Two cocrystal structures of actinorhodin polyketide ketoreductase (act KR) were solved to 2.3 A with either the cofactor NADP(+) or NADPH bound. The monomer fold is a highly conserved Rossmann fold. Subtle differences between structures of act KR and fatty acid KRs fine-tune the tetramer interface and substrate binding pocket. Comparisons of the NADP(+)- and NADPH-bound structures indicate that the alpha6-alpha7 loop region is highly flexible. The intricate proton-relay network in the active site leads to the proposed catalytic mechanism involving four waters, NADPH, and the active site tetrad Asn114-Ser144-Tyr157-Lys161. Acyl carrier protein and substrate docking models shed light on the molecular basis of KR regio- and stereoselectivity, as well as the differences between aromatic polyketide and fatty acid biosyntheses. Sequence comparison indicates that the above features are highly conserved among aromatic polyketide KRs. The structures of act KR provide an important step toward understanding aromatic PKS and will enhance our ability to design novel aromatic polyketide natural products with different reduction patterns.


  • 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
Putative ketoacyl reductase
A, B
261Streptomyces coelicolorMutation(s): 0 
Gene Names: actIII
EC: 1.3.1
UniProt
Find proteins for P16544 (Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145))
Explore P16544 
Go to UniProtKB:  P16544
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16544
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.211 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.61α = 90
b = 104.61β = 90
c = 124.25γ = 120
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata 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: 2004-12-14
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations