7AGS

Structure of the AcylTransferase domain of Mycocerosic Acid Synthase from Mycobacterium tuberculosis acylated MethylMalonyl-CoenzymeA

7AGS の概要

• エントリーDOI: 10.2210/pdb7ags/pdb
• 関連するPDBエントリー: 7AGP 7AGQ 7AGR 7AGT 7AGU
• 分子名称: Mycocerosic acid synthase, METHYLMALONIC ACID (3 entities in total)
• 機能のキーワード: mycocerosic acid synthase, acyltransferase domain, polyketide synthase, mycobacterium tuberculosis, methylmalonyl-coenzyme a, transferase
• 由来する生物種: Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93058.92

構造登録者

Brison, Y.,Mourey, L.,Maveyraud, L. (登録日: 2020-09-23, 公開日: 2020-12-16, 最終更新日: 2024-01-31)

主引用文献

Grabowska, A.D.,Brison, Y.,Maveyraud, L.,Gavalda, S.,Faille, A.,Nahoum, V.,Bon, C.,Guilhot, C.,Pedelacq, J.D.,Chalut, C.,Mourey, L.
Molecular Basis for Extender Unit Specificity of Mycobacterial Polyketide Synthases.
Acs Chem.Biol., 15:3206-3216, 2020

PubMed Abstract: is the causative agent of the tuberculosis disease, which claims more human lives each year than any other bacterial pathogen. and other mycobacterial pathogens have developed a range of unique features that enhance their virulence and promote their survival in the human host. Among these features lies the particular cell envelope with high lipid content, which plays a substantial role in mycobacterial pathogenicity. Several envelope components of and other mycobacteria, e.g., mycolic acids, phthiocerol dimycocerosates, and phenolic glycolipids, belong to the "family" of polyketides, secondary metabolites synthesized by fascinating versatile enzymes-polyketide synthases. These megasynthases consist of multiple catalytic domains, among which the acyltransferase domain plays a key role in selecting and transferring the substrates required for polyketide extension. Here, we present three new crystal structures of acyltransferase domains of mycobacterial polyketide synthases and, for one of them, provide evidence for the identification of residues determining extender unit specificity. Unravelling the molecular basis for such specificity is of high importance considering the role played by extender units for the final structure of key mycobacterial components. This work provides major advances for the use of mycobacterial polyketide synthases as potential therapeutic targets and, more generally, contributes to the prediction and bioengineering of polyketide synthases with desired specificity.

PubMed: 33237724
DOI: 10.1021/acschembio.0c00772

実験手法

X-RAY DIFFRACTION (3.1 Å)