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An unconventional family 1 uracil DNA glycosylase in Nitratifractor salsuginis
Author(s) -
Li Jing,
Chen Ran,
Yang Ye,
Zhang Zhemin,
Fang GuangChen,
Xie Wei,
Cao Weiguo
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14285
Subject(s) - uracil dna glycosylase , dna glycosylase , uracil , salt bridge , dna , biochemistry , protein data bank (rcsb pdb) , chemistry , biology , tyrosine , dna repair , mutant , gene
The uracil DNA glycosylase superfamily consists of at least six families with a diverse specificity toward DNA base damage. Family 1 uracil N ‐glycosylase ( 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 UNG s. 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. Database Structure data are available in the PDB under accession numbers 5X3G and 5X3H .