4JAO

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

4JAO の概要

• エントリーDOI: 10.2210/pdb4jao/pdb
• 関連するPDBエントリー: 4JAP 4JAQ 4JAR 4JAT 4JD3
• 分子名称: Alpha-pyrone synthesis polyketide synthase-like Pks11, PALMITIC ACID, (2S)-2-methylheptadecan-1-ol, ... (4 entities in total)
• 機能のキーワード: lipid biosynthesis, structural genomics, enzyme function initiative, ketosynthase enzyme, alkylpyrone synthesis, transferase, mycobacterium tuberculosis structural proteomics project, xmtb
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 151778.42

構造登録者

Gokulan, K.,Sacchettini, J.C.,Mycobacterium Tuberculosis Structural Proteomics Project (XMTB) (登録日: 2013-02-18, 公開日: 2013-04-24, 最終更新日: 2024-11-20)

主引用文献

Gokulan, K.,O'Leary, S.E.,Russell, W.K.,Russell, D.H.,Lalgondar, M.,Begley, T.P.,Ioerger, T.R.,Sacchettini, J.C.
Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones.
J.Biol.Chem., 288:16484-16494, 2013

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.

PubMed: 23615910
DOI: 10.1074/jbc.M113.468892

実験手法

X-RAY DIFFRACTION (2.05 Å)