Structure and Catalytic Mechanism of a SET Domain Protein Methyltransferase

✍ Scribed by Raymond C. Trievel; Bridgette M. Beach; Lynnette M.A. Dirk; Robert L. Houtz; James H. Hurley

• Book ID: 117269276
• Publisher: Elsevier Science
• Year: 2002
• Tongue: English
• Weight: 858 KB
• Volume: 111
• Category: Article
• ISSN: 0092-8674
• DOI: 10.1016/s0092-8674(02)01000-0

✦ Synopsis

Protein lysine methylation by SET domain enzymes regulates chromatin structure, gene silencing, transcriptional activation, plant metabolism, and other processes. The 2.6 A resolution structure of Rubisco large subunit methyltransferase in a pseudo-bisubstrate complex with S-adenosylhomocysteine and a HEPES ion reveals an all-beta architecture for the SET domain embedded within a larger alpha-helical enzyme fold. Conserved regions of the SET domain bind S-adenosylmethionine and substrate lysine at two sites connected by a pore. We propose that methyl transfer is catalyzed by a conserved Tyr at a narrow pore connecting the sites. The cofactor enters by a "back door" on the opposite side of the enzyme from substrate, promoting highly specific protein recognition and allowing addition of multiple methyl groups.