Hua Yuan, Dorine Rossetto, Hestia Mellert, Weiwei Dang, Madhusudan Srinivasan, Jamel Johnson, Santosh Hodawadekar, Emily C Ding, Kaye Speicher, Nebiyu Abshiru, Rocco Perry, Jiang Wu, Chao Yang, Y George Zheng, David W Speicher, Pierre Thibault, Alain Verreault, F Bradley Johnson, Shelley L Berger, Rolf Sternglanz, Steven B McMahon, Jacques Côté, Ronen Marmorstein
The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site...
January 4, 2012: EMBO Journal