Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 23, pp 2755–2763

SET domain protein lysine methyltransferases: Structure, specificity and catalysis

Review

DOI: 10.1007/s00018-006-6274-5

Cite this article as:
Qian, C. & Zhou, M.M. Cell. Mol. Life Sci. (2006) 63: 2755. doi:10.1007/s00018-006-6274-5

Abstract.

Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins that contain the evolutionarily conserved SET domain and plays a fundamental role in epigenetic regulation of gene activation and silencing in all eukaryotes. The recently determined three-dimensional structures of the SET domains from chromosomal proteins reveal that the core SET domain structure contains a two-domain architecture, consisting of a conserved anti-parallel β-barrel and a structurally variable insert that surround a unusual knot-like structure that comprises the enzyme active site. These structures of the SET domains, either in the free state or when bound to cofactor S-adenosyl-L-homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate complex, further yield the structural insights into the molecular basis of the substrate specificity, methylation multiplicity and the catalytic mechanism of histone lysine methylation.

Keywords.

SET domainhistone lysine methylationstructure-functionchromatin modifications

Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  1. 1.Department of Molecular Physiology and Biophysics, Mount Sinai School of MedicineNew York UniversityNew YorkUSA