Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294

• Type of Material: Article
• Authors: Yanqi Chang, Emory University; Xing Zhang, Emory University; John Horton, Emory University; Anup K. Upadhyay, Emory University; Astrid Spannhoff, University of Texas; Jin Liu, Emory University; James P Snyder, Emory University; Mark T. Bedford, University of Texas; Xiaodong Cheng, Emory University
• Language: English
• Date: 2009-03
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Nature America, Inc. All rights reserved
• Final Published Version (URL): http://www.nature.com/nsmb/journal/v16/n3/full/nsmb.1560.html
• Title of Journal or Parent Work: Nature Structural & Molecular Biology
• ISSN: 1545-9993
• Volume: 16
• Issue: 3
• Start Page: 312
• End Page: 317
• Grant/Funding Information: This work was supported by grant GM068680 to X.C. from the National Institutes of Health and the Welch Foundation Grant G-1495 to MTB.
• Research Categories: Chemistry, Biochemistry

Abstract

We present the crystal structure of the catalytic SET domain of G9a-like protein (GLP) in complex with BIX-01294. The inhibitor is bound in the substrate peptide groove at the location where the histone H3 residues (Lys4 to Arg8) N-terminal to the target lysine would occupy. The inhibitor is positioned in place by residues specific for G9a and GLP using planar stacking contacts, polar hydrogen bonds and van der Waals interactions.