Figure 4: Inhibition studies of the synthetic sansanmycin analogues against Mtb MurX. | Nature Communications

Figure 4: Inhibition studies of the synthetic sansanmycin analogues against Mtb MurX.

From: Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis

Figure 4

(a) Reactions catalysed by Mtb MurX to generate lipid I and Mtb MurG to generate lipid II. (b) Exemplar TLC assay from Mtb mc2 6230 membranes for the inhibition of Mtb MurX–MurG by dihydrosansanmycin analogue 37 (IC50=41 nM). Positive control=pacidamycin D19 and tunicamycin. Ala, alanine; Glu, glutamate; mA2P, meso-diaminopimelic acid. Product of MurX=decaprenyldiphosphoryl-MurNAc-pentapeptide (lipid I), product of MurG=decaprenyldiphosphoryl-MurNAc-pentapeptide-GlcNAc (lipid II), product of WecA=decaprenyldiphosphoryl-GlcNAc. (c) Inhibition assay of Mtb MurX with dihydrosansanmycin analogue 37 (IC50=16 nM) using dansylated UDP-MurNAc pentapeptide as substrate. Km(app) UDP-MurNAc-pentapeptide=51±4 μM and Vmax(app)=69±1.9 μM min−1; Km(app) polyisoprenylphosphate=56±9 μg ml−1 (Supplementary Figs 40 and 41). Positive control tunicamycin: IC50=189 nM (Supplementary Fig. 46).

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