YibK methyltransferase (knot protein) complexed with an inhibitor (AdoHcy)
Haemophilus influenzae (bacteria)
Expression of genes from DNA to RNA (transcription) and then to proteins (translation) is a highly regulated process. It is regulated at various levels during transcription and translation. DNA methylation is a form of regulation of gene expression. It involves the inactivation of a gene by methylating the cytosine (C) nucleotides in the sequence CG in the DNA, particularly in vertebrates. Methyltransferases are the enzymes that perform this methylation. In addition to methylation of DNA, methyltransferases also methylate small molecules and proteins. Methyltransferases require the cofactor S-adenosylmethionine (AdoMet) as a methyl donor in order to perform methylation. AdoMet changes to S-adenosylhomocysteine (AdoHcy) on donating its methyl group. AdoHcy is a potent inhibitor of most methyltransferases. The above structure is that of the YibK Methyltransferase from Haemophilus influenzae.
The structure here is that of the complex of a YibK Methyltransferase with AdoHcy (The structure without AdoHcy shows in xPSSS:1J85). The molecule is a single domain protein that adopts an alpha/beta fold with an all-parallel beta sheet. However, it has a topology different from that of classical methyltransferases. It forms a knot which is the binding crevice for the cofactor. The nature of AdoHcy binding is also different, being in a bent conformation rather than an extended one. It has been proposed that this methyltransferase is remotely related to the rRNA/tRNA methyltransferases of the spoU sequence family and that the spoU sequence family contains the same core domain as shown above with the addition of an extra domain for substrate recognition.
Protein Data Bank (PDB)
author: Ashwini Patil