IBB PAS Repository

Biosynthesis of a water-soluble lipid I analogue and a convenient assay for translocase I

Siricilla, Shajila and Mitachi, Katsuhiko and Skorupinska-Tudek, Karolina and Swiezewska, Ewa and Kurosu, Michio (2014) Biosynthesis of a water-soluble lipid I analogue and a convenient assay for translocase I. Analytical Biochemistry, 461 (C). pp. 36-45.

[img] Microsoft Word

Official URL: http://www.sciencedirect.com/science/article/pii/S...


Translocase I (MraY/MurX) is an essential enzyme in growth of the vast majority of bacteria that catalyzes the transformation from UDP-MurNAc-pentapeptide (Park’s nucleotide) to prenyl-MurNAc-pentapeptide (lipid I), the first membrane-anchored peptidoglycan precursor. MurX has received considerable attention in the development of new tuberculosis (TB) drugs due to the fact that the MurX inhibitors kill exponentially growing Mycobacterium tuberculosis (Mtb) much faster than clinically used TB drugs. Lipid I isolated from Mtb contains the C50-prenyl unit that shows very poor water solubility; thus, this chemical characteristic of lipid I renders MurX enzyme assays impractical for screening and lacks reproducibility of the enzyme assays.Wehave established a scalable chemical synthesis of Park’s nucleotide-Ne-dansylthiourea 2 that can be used as a MurX enzymatic substrate to form lipid I analogues. In our investigation of the minimumstructure requirement of the prenyl phosphate in the MraY/MurX-catalyzed lipid I analogue synthesis with 2,we found that neryl phosphate (C10 phosphate) can be recognized by MraY/MurX to generate the water-soluble lipid I analogue in quantitative yield under the optimized conditions. Here, we report a rapid and robust analytical method for quantifying MraY/MurX inhibitory activity of library molecules

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Lipid Biochemistry
ID Code:742
Deposited By: Ewa Swiezewska
Deposited On:18 Dec 2014 10:45
Last Modified:18 Dec 2014 10:45

Repository Staff Only: item control page