Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision

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Title
Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision
Author(s)
Woo-Chan Ahn; S Aroli; J H Kim; Jeong Hee Moon; Ga Seal Lee; Min-Ho Lee; P B Sang; B H Oh; U Varshney; Eui-Jeon Woo
Bibliographic Citation
Nature Chemical Biology, vol. 15, no. 6, pp. 607-614
Publication Year
2019
Abstract
Uracil DNA glycosylases (UDGs) are important DNA repair enzymes that excise uracil from DNA, yielding an abasic site. Recently, UdgX, an unconventional UDG with extremely tight binding to DNA containing uracil, was discovered. The structure of UdgX from Mycobacterium smegmatis in complex with DNA shows an overall similarity to that of family 4 UDGs except for a protruding loop at the entrance of the uracil-binding pocket. Surprisingly, H109 in the loop was found to make a covalent bond to the abasic site to form a stable intermediate, while the excised uracil remained in the pocket of the active site. H109 functions as a nucleophile to attack the oxocarbenium ion, substituting for the catalytic water molecule found in other UDGs. To our knowledge, this change from a catalytic water attack to a direct nucleophilic attack by the histidine residue is unprecedented. UdgX utilizes a unique mechanism of protecting cytotoxic abasic sites from exposure to the cellular environment.
ISSN
1552-4450
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41589-019-0289-3
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > Core Facility Management Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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