Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides.

• Type of Material: Article
• Authors: Xing Zhang, Emory University; Xiaodong Cheng, Emory University
• Language: English
• Date: 2003-05-01
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2003 Cell Press. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/S0969-2126(03)00071-6
• Title of Journal or Parent Work: Structure
• ISSN: 0969-2126
• Volume: 11
• Issue: 5
• Start Page: 509
• End Page: 520
• Grant/Funding Information: These studies were supported in part by the National Institutes of Health (GM61355).
• Keywords: SACCHAROMYCES-CEREVISIAE; Cell Biology; RECEPTOR; Science & Technology; Biophysics; SPECIFICITY; Biochemistry & Molecular Biology; SUBCELLULAR-LOCALIZATION; ENZYME; METHYLATION; IDENTIFICATION; Life Sciences & Biomedicine; N-METHYLTRANSFERASE; MOLECULAR-WEIGHT; N-METHYLTRANSFERASE-1
• Research Categories: Health Sciences, General; Chemistry, Biochemistry

Abstract

PRMT1 is the predominant type I protein arginine methyltransferase in mammals and highly conserved among all eukaryotes. It is essential for early postimplantation development in mouse. Here we describe the crystal structure of rat PRMT1 in complex with the reaction product AdoHcy and a 19 residue substrate peptide containing three arginines. The results reveal a two-domain structure - an AdoMet binding domain and a barrel-like domain - with the active site pocket located between the two domains. Mutagenesis studies confirmed that two active site glutamates are essential for enzymatic activity, and that dimerization of PRMT1 is essential for AdoMet binding. Three peptide binding channels are identified: two are between the two domains, and the third is on the surface perpendicular to the strands forming the β barrel.