Chemogenetic analysis of human protein methyltransferases.

摘要: A survey of the human genome was performed to understand constituency protein methyltransferases (both arginine and lysine methyltransferases) relatedness their catalytic domains. We identified 51 methyltransferase proteins based on similarity canonical Drosophila Su(var)3-9, enhancer zeste (E(z)), trithorax (trx) domain. Disruptor telomeric silencing-1-like, a known methyltransferase, did not fit within family, but group with methyltransferases, along 44 other proteins, including METTL NOP2/Sun domain family proteins. show that representative METTL, METTL11A, demonstrates activity as histone methyltransferase. also solved co-crystal structures disruptor silencing-1-like S-adenosylmethionine S-adenosylhomocysteine bound in its active site. The conformation both ligands is virtually identical found distinct from seen methyltransferases. have developed biochemical assays for 11 members target class profiled affinity three these enzymes: common methyl-donating substrate S-adenosylmethionine; reaction product S-adenosylhomocysteine; natural sinefungin. each mapped onto trees reveal patterns ligand recognition by enzymes.