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PDBsum entry 4jao

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protein ligands Protein-protein interface(s) links
Transferase PDB id
4jao
Jmol
Contents
Protein chains
352 a.a.
Ligands
PLM ×2
JAO ×2
Waters ×385
PDB id:
4jao
Name: Transferase
Title: Crystal structure of mycobacterium tuberculosis pks11 reveal intermediates in the synthesis of methyl-branched alkylpyro
Structure: Alpha-pyrone synthesis polyketide synthase-like p chain: d, c, b, a. Synonym: alpha-pyrone synthesis polyketide synthase type ii chalcone synthase-like protein, chs-like. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Strain: h37rv. Gene: pks11, rv1665, mt1705. Expressed in: mycobacterium smegmatis. Expression_system_taxid: 1772
Resolution:
2.05Å     R-factor:   0.214     R-free:   0.271
Authors: K.Gokulan,J.C.Sacchettini,Mycobacterium Tuberculosis Structu Proteomics Project (Xmtb)
Key ref: K.Gokulan et al. (2013). Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones. J Biol Chem, 288, 16484-16494. PubMed id: 23615910 DOI: 10.1074/jbc.M113.468892
Date:
18-Feb-13     Release date:   24-Apr-13    
PROCHECK
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 Headers
 References

Protein chains
Pfam  
P9WPF2  (PKS11_MYCTO) -  Alpha-pyrone synthesis polyketide synthase-like Pks11
Seq:
Struc:
353 a.a.
352 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
DOI no: 10.1074/jbc.M113.468892 J Biol Chem 288:16484-16494 (2013)
PubMed id: 23615910  
 
 
Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones.
K.Gokulan, S.E.O'Leary, W.K.Russell, D.H.Russell, M.Lalgondar, T.P.Begley, T.R.Ioerger, J.C.Sacchettini.
 
  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.