Extended Data Fig. 5: TMA does not bind with kinases ANKK1, HIPK2, JAK2, and NDR1 identified as candidates in the kinome screen, but makes significant contact with IRAK4. | Nature Metabolism

Extended Data Fig. 5: TMA does not bind with kinases ANKK1, HIPK2, JAK2, and NDR1 identified as candidates in the kinome screen, but makes significant contact with IRAK4.

From: Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control

Extended Data Fig. 5

(a) Confirmation of a physical interaction between TMA and IRAK4 using TMA at concentrations ranging from 0.1 nM to 100 µM, resulting in a dissociation constant (Kd) of 14 nM. (b–e) Physical interaction test between TMA and the four hits identified using a kinome screen, using TMA concentrations ranging from 0.1 nM to 100 µM for (b) ANKK1, (c) HIPK2, (d) JAK2 and (e) NDR1. For (b-e) N = 2 biological repeats. IRAK4 kinase activity is not significantly inhibited by choline (f), TMAO (g) or DMB (h), while TMA does not have any inhibitory effect on IRAK-1 kinase activity (average of N = 2 biological repeats) (i). (j, k) Phosphorylation for pThr183/Tyr185SAPK/JNK/SAPK/JNK (j) and pThr180/Tyr182p38MAPK/p38MAPK (k) densitometric ratios, represented by each dot. Data are means ± s.e.m. One-way ANOVA followed by Tukey’s post hoc tests (superscript letters for factor levels P < 0.05) on log-transformed data. Source data are provided.

Source data

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