5x3h
The Y81G mutant of the UNG crystal structure from Nitratifractor salsuginisThe Y81G mutant of the UNG crystal structure from Nitratifractor salsuginis
Structural highlights
FunctionPublication Abstract from PubMedThe 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. See AlsoReferences
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