Structure of the Siz/PIAS SUMO E3 Ligase Siz1 and determinants required for SUMO modification of PCNA Journal Article

   

Authors:	Yunus, A. A.; Lima, C. D.
Article Title:	Structure of the Siz/PIAS SUMO E3 Ligase Siz1 and determinants required for SUMO modification of PCNA
Abstract:	Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The X-ray structure of an active Siz1 ligase revealed an elongated tripartite architecture comprised of an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure-based mutational analysis and biochemical studies show that the SP-RING and SP-CTD are required for activation of the E2∼SUMO thioester, while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a nonconsensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1. Mutational analysis of Siz1 and PCNA revealed surfaces on both proteins that are required for efficient SUMO modification of PCNA in vitro and in vivo. © 2009 Elsevier Inc. All rights reserved.
Keywords:	controlled study; unclassified drug; mutation; nonhuman; protein conformation; proteins; ubiquitin protein ligase; carboxy terminal sequence; in vivo study; enzyme activation; in vitro study; structure-activity relationship; mutational analysis; dna; amino acid sequence; molecular sequence data; protein processing, post-translational; amino terminal sequence; kinetics; saccharomyces cerevisiae; sequence alignment; recombinant proteins; crystal structure; models, molecular; crystallography, x-ray; mutagenesis, site-directed; protein structure, tertiary; saccharomyces cerevisiae proteins; cycline; zinc; structure analysis; x ray crystallography; ubiquitin protein ligase e3; enzyme structure; ring finger motif; sumoylation; ubiquitin-conjugating enzymes; catalytic domain; ubiquitin-protein ligases; lysine; thioester; small ubiquitin-related modifier proteins; siz1 ligase; ubiquitin protein ligase e2; proliferating cell nuclear antigen
Journal Title:	Molecular Cell
Volume:	35
Issue:	5
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2009-09-11
Start Page:	669
End Page:	682
Language:	English
DOI:	10.1016/j.molcel.2009.07.013
PUBMED:	19748360
PROVIDER:	scopus
PMCID:	PMC2771690
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-69749124557&partnerID=40&md5=9d10a75b520f8d0328de145fb43be3fd
Notes:	--- - "Cited By (since 1996): 6" - "Export Date: 30 November 2010" - "CODEN: MOCEF" - "Source: Scopus"

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