Back

Discovery of Chirally-dependent Protein O-2-Hydroxyglutarylation by D2HG and L2HG

Zhang, Z.; Liu, Y.-K.; Luo, Z.; Wu, M.-J.; Evans, C. N.; Qu, Z.; Xue, F.; Zhang, Z.-Y.; Parkinson, E. I.; Bardeesy, N.; Tao, W. A.

2025-01-27 biochemistry
10.1101/2025.01.24.634716 bioRxiv
Show abstract

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are common in multiple types of human cancer, leading to the accumulation of D-2-hydroxyglutarate (D2HG) and the promotion of tumorigenesis1. Here we discovered a novel O-2- hydroxyglutarylation by D2HG using chemical proteomics and further revealed distinct chiral preferences for D/L2HG modifications. Notably, we identified two kinases, MRCKA and SLK, modified by D2HG and L2HG respectively, and detected reduced phosphorylation of their substrates, suggesting an inhibitory effect of D/L 2HG modifications on the kinases activity.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.