Binding of adenosine-based ligands to the MjDim1 rRNA methyltransferase: implications for reaction mechanism and drug design.

摘要: The KsgA/Dim1 family of proteins is intimately involved in ribosome biogenesis all organisms. These enzymes share the common function dimethylating two adenosine residues near 3'-OH end small subunit rRNA; orthologs three kingdoms, along with eukaryotic organelles, have evolved additional functions rRNA processing, assembly, and, surprisingly, transcription mitochondria. methyltransferase reaction intriguingly elaborate. can bind to naked but cannot methylate their target bases until a subset ribosomal bound and nascent has reached certain level maturity. Once this threshold reached, enzyme must stabilize adenosines into active site at separate times methyl groups be transferred each adenosine, concomitant exchanges product S-adenosyl-l-homocysteine donor substrate S-adenosyl-l-methionine. A detailed molecular understanding mechanism currently lacking. Structural analysis interactions between will aid understanding. Here we present structure KsgA from Methanocaldococcus jannaschii complex several ligands, including first S-adenosyl-l-methionine catalytically productive way. We also discuss inability thus far determine its site.