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Publication Abstract from PubMed

The uracil DNA glycosylase superfamily consists of at least six families with a diverse specificity towards DNA base damage. Family 1 UNG exhibits exclusive specificity on uracil-containing DNA. Here, we report a family 1 UNG homolog from Nitratifractor salsuginis with distinct biochemical features that differentiate it from conventional family 1 UNGs. Globally, the crystal structure of N. salsuginis UNG shows a few additional secondary structural elements. Biochemical and enzyme kinetic analysis, coupled with structural determination, molecular modeling and molecular dynamics simulations, shows that N. salsuginis UNG contains a salt bridge network that plays an important role in DNA backbone interactions. Disruption of the amino acid residues involved in the salt bridges greatly impedes the enzymatic activity. A tyrosine residue in motif 1 (GQDPY) is one of the distinct sequence features setting family 1 UNG apart from other families. The crystal structure of Y81G mutant indicates that several subtle changes may account for its inactivity. Unlike the conventional family 1 UNG enzymes, N. salsuginis UNG is not inhibited by Ugi, a potent inhibitor specific for family 1 UNG. This study underscores the diversity of paths that a uracil DNA glycosylase may take to acquire its unique structural and biochemical properties during evolution. This article is protected by copyright. All rights reserved.

An Unconventional Family 1 Uracil DNA Glycosylase in Nitratifractor salsuginis.,Li J, Chen R, Yang Y, Zhang Z, Fang GC, Xie W, Cao W FEBS J. 2017 Oct 4. doi: 10.1111/febs.14285. PMID:28977725^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.