User:Lauryn Padgett/Sandbox 1

Structure

Overall Secondary Structure

Due to the composition of its secondary structure, KMT is an alpha-beta protein . The helical composition includes 3 , with two residing in the SET domain and one in the C-terminal domain. The alpha helices in the SET domain are two turns while the C-terminal helix is by far the largest with 4 turns. There are also 2 in the SET domain which are each one turn. There are 21 total which reside in the N-terminal domain and the SET domain. The beta strands are primarily anti-parallel and multiple antiparallel strands are connected by and beta turns.

The of the protein is essential for the binding and stabilization of the cofactor. The

SET Domain

Cofactor

Active Site

Mechanism

Function

Inhibitor

Sinefungin is a potent methyltransferase inhibitor that is a natural nucleoside isolated from the Streptomyces species. Also referred to as adenosyl-ornithine, it is the delta (5’ adenosyl) derivative of ornithine and a structural analog of S-adenosylmethionine. Sinefungin is more stable bound in the active site than SAM due to the ability to create two additional hydrogen bonds to its amine group that are not possible with SAM’s sulfur. Sinefungin has been used experimentally to inhibit the SET 7/9 protein on peritoneal fibrosis in mice and in human peritoneal mesothelial cells Cite error: Invalid <ref> tag; refs with no content must have a name. SET 7/9 is involved in peritoneal fibrosis because it mono-methylates H3K4, which activates the transcription of fibrosis related genes. The administration of Sinefungin to mice correlated with decreasing levels of methylated H3K4 (H3K4me1) protein, as well as suppressed cell accumulation and thickening in methylglyoxial peritoneal fibrosis. The decreased levels of H3K4me1 suggest that the methylation of H3K4 was inhibited by Sinefungin.