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PMID: 12372303 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Structure and catalytic mechanism of a SET domain protein methyltransferase.

Cell ·Vol. 111 ·No. 1 ·2002-10-04 ·Pages 91-103

Trievel RC, Beach BM, Dirk LM, Houtz RL, Hurley JH

Abstract

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.

MeSH Terms

Amino Acid Motifs Amino Acid Sequence Binding Sites Chromatin/chemistry Conserved Sequence DNA Mutational Analysis DNA-Binding Proteins/chemistry Dimerization Dose-Response Relationship, Drug Drosophila Proteins/chemistry Electrons Gene Silencing HEPES/pharmacology Histones/chemistry Kinetics Ligands Lysine/chemistry Models, Chemical Models, Molecular Molecular Sequence Data Nuclear Proteins/chemistry Peas/enzymology Polycomb Repressive Complex 2 Protein Binding Protein Methyltransferases/chemistry Protein Structure, Secondary Protein Structure, Tertiary Repressor Proteins/chemistry Spinacia oleracea/enzymology Substrate Specificity Transcription Factors Transcriptional Activation Tyrosine/chemistry

Chemicals

Chromatin DNA-Binding Proteins Drosophila Proteins Histones Ligands Nuclear Proteins Repressor Proteins Transcription Factors Trl protein, Drosophila Tyrosine Protein Methyltransferases E(z) protein, Drosophila Polycomb Repressive Complex 2 Lysine HEPES

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Trievel Raymond C

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Beach Bridgette M

Dirk Lynnette M A

Houtz Robert L

Hurley James H

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(02)01000-0

Published

2002-10-04

Pages

91-103

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(02)01000-0 View journal details

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Structure and catalytic mechanism of a SET domain protein methyltransferase.

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