Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT

Raymond C. Trievel, E. Megan Flynn, Robert L. Houtz, James H. Hurley

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

SET domain protein methyltransferases catalyze the transfer of methyl groups from the cofactor S-adenosylmethionine (AdoMet) to specific lysine residues of protein substrates, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex. The crystal structures of pea Rubisco large subunit methyltransferase (LSMT) in ternary complexes with either lysine or ε-N-methyllysine (MeLys) and the product S-adenosylhomocysteine (AdoHcy) were determined to resolutions of 2.65 and 2.55 Å, respectively. The ζ-methyl group of MeLys is bound to the enzyme via carbon-oxygen hydrogen bonds that play a key role in catalysis. The methyl donor and acceptor are aligned in a linear geometry for SN2 nucleophilic transfer of the methyl group during catalysis. Differences in hydrogen bonding between the MeLys ε-amino group and Rubisco LSMT and SET7/9 explain why Rubisco LSMT generates multiply methylated Lys, wheras SET7/9 generates only MeLys.

Original languageEnglish
Pages (from-to)545-552
Number of pages8
JournalNature Structural Biology
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2003

Bibliographical note

Funding Information:
We would like to thank S. Gamblin for SET7/9–AdoHcy–histone H3 ternary complex coordinates, and D. Engelman and G. Felsenfeld for insightful discussions. Research by R.L.H. and E.M.F. was supported by the DOE, Division of Energy Biosciences.

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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