Active site remodelling accompanies thioester bond formation in the SUMO E1
Shaun K. Olsen,
Allan D. Capili,
Xuequan Lu,
Derek S. Tan () and
Christopher D. Lima ()
Additional contact information
Shaun K. Olsen: Structural Biology and,
Allan D. Capili: Structural Biology and,
Xuequan Lu: Molecular Pharmacology and Chemistry Programs, Sloan-Kettering Institute, New York, New York 10065, USA
Derek S. Tan: Molecular Pharmacology and Chemistry Programs, Sloan-Kettering Institute, New York, New York 10065, USA
Christopher D. Lima: Structural Biology and,
Nature, 2010, vol. 463, issue 7283, 906-912
Abstract:
Abstract E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 Å, respectively. These structures show that side chain contacts to ATP·Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.
Date: 2010
References: Add references at CitEc
Citations: View citations in EconPapers (3)
Downloads: (external link)
https://www.nature.com/articles/nature08765 Abstract (text/html)
Access to the full text of the articles in this series is restricted.
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:463:y:2010:i:7283:d:10.1038_nature08765
Ordering information: This journal article can be ordered from
https://www.nature.com/
DOI: 10.1038/nature08765
Access Statistics for this article
Nature is currently edited by Magdalena Skipper
More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().