4JD3

Crystal Structure of Mycobacterium tuberculosis PKS11 Reveals Intermediates in the Synthesis of Methyl-branched Alkylpyrones


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.294 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.199 

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Literature

Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones.

Gokulan, K.O'Leary, S.E.Russell, W.K.Russell, D.H.Lalgondar, M.Begley, T.P.Ioerger, T.R.Sacchettini, J.C.

(2013) J Biol Chem 288: 16484-16494

  • DOI: https://doi.org/10.1074/jbc.M113.468892
  • Primary Citation of Related Structures:  
    4JAO, 4JAP, 4JAQ, 4JAR, 4JAT, 4JD3

  • PubMed Abstract: 

    PKS11 is one of three type III polyketide synthases (PKSs) identified in Mycobacterium tuberculosis. Although many PKSs in M. tuberculosis have been implicated in producing complex cell wall glycolipids, the biological function of PKS11 is unknown. PKS11 has previously been proposed to synthesize alkylpyrones from fatty acid substrates. We solved the crystal structure of M. tuberculosis PKS11 and found the overall fold to be similar to other type III PKSs. PKS11 has a deep hydrophobic tunnel proximal to the active site Cys-138 to accommodate substrates. We observed electron density in this tunnel from a co-purified molecule that was identified by mass spectrometry to be palmitate. Co-crystallization with malonyl-CoA (MCoA) or methylmalonyl-CoA (MMCoA) led to partial turnover of the substrate, resulting in trapped intermediates. Reconstitution of the reaction in solution confirmed that both co-factors are required for optimal activity, and kinetic analysis shows that MMCoA is incorporated first, then MCoA, followed by lactonization to produce methyl-branched alkylpyrones.


  • Organizational Affiliation

    Departments of Biochemistry and Biophysics, College Station, Texas 77843.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-pyrone synthesis polyketide synthase-like Pks11A,
B [auth C],
C [auth B],
D
353Mycobacterium tuberculosisMutation(s): 1 
Gene Names: pks11Rv1665MT1705
EC: 2.3.1
UniProt
Find proteins for P9WPF3 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WPF3 
Go to UniProtKB:  P9WPF3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WPF3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.294 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.199 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.166α = 90
b = 48.863β = 97.82
c = 194.473γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MLPHAREphasing
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-24
    Type: Initial release
  • Version 1.1: 2014-05-21
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations