4jao | pdb_00004jao

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

spinqualitylabelsall models 4jao, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jao is a 4 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.05Å Ligands: JAO, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PKS11_MYCTU Involved in the biosynthesis of tri- and tetraketide alpha-pyrones. Pks18 catalyzes the extension of medium- and long-chain aliphatic acyl-CoA substrates by using malonyl-CoA as an extender molecule to synthesize polyketide products. Publication Abstract from PubMed 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. Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones.,Gokulan K, O'Leary SE, Russell WK, Russell DH, Lalgondar M, Begley TP, Ioerger TR, Sacchettini JC J Biol Chem. 2013 Jun 7;288(23):16484-94. doi: 10.1074/jbc.M113.468892. Epub 2013, Apr 24. PMID:23615910 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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