Potential double-flipping mechanism by E. coli MutY

Paul G. House, David E. Volk, Varatharasa Thiviyanathan, Raymond C. Manuel, Bruce A. Luxon, David G. Gorenstein, R. Stephen Lloyd

Research output: Chapter in Book/Report/Conference proceedingChapter

12 Scopus citations


To understand the structural basis of the recognition and removal of specific mismatched bases in double-stranded DNAs by the DNA repair glycosylase MutY, a series of structural and functional analyses have been conducted. MutY is a 39-kDa enzyme from Escherichia coli, which to date has been refractory to structural determination in its native, intact conformation. However, following limited proteolytic digestion, it was revealed that the MutY protein is composed of two modules, a 26-kDa domain that retains essential catalytic function (designated p26MutY) and a 13-kDa domain that is implicated in substrate specificity and catalytic efficiency. Several structures of the 26-kDa domain have been solved by X-ray crystallographic methods to a resolution of up to 1.2 Å. The structure of a catalytically incompetent mutant of p26MutY complexed with an adenine in the substrate-binding pocket allowed us to propose a catalytic mechanism for MutY. Since reporting the structure of p26MutY, significant progress has been made in solving the solution structure of the noncatalytic C-terminal 13-kDa domain of MutY by NMR spectroscopy. The topology and secondary structure of this domain are very similar to that of MutT, a pyrophosphohydrolase. Molecular modeling techniques employed to integrate the two domains of MutY with DNA suggest that MutY can wrap around the DNA and initiate catalysis by potentially flipping adenine and 8-oxoguanine out of the DNA helix.

Original languageEnglish (US)
Title of host publicationBase Excesion Repair
PublisherAcademic Press Inc.
Number of pages16
ISBN (Print)0125400683, 9780125400688
StatePublished - 2001
Externally publishedYes

Publication series

NameProgress in Nucleic Acid Research and Molecular Biology
ISSN (Print)0079-6603

ASJC Scopus subject areas

  • Molecular Biology


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