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Structural similarities between MutT and the C-terminal domain of MutY
D E Volk1, P G House, V Thiviyanathan
1Sealy Center for Structural Biology and Sealy Center for Molecular Sciences, Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555, USA. david@nmr.utmb.edu
Abstract:
One of the functions of MutY from Escherchia coli is removal of adenine mispaired with 7,8-dihydro-8-oxoguanine (8-oxoG), a common lesion in oxidatively damaged DNA. MutY is composed of two domains: the larger N-terminal domain (p26) contains the catalytic properties of the enzyme while the C-terminal domain (p13) affects substrate recognition and enzyme turnover. On the basis of sequence analyses, it has been recently suggested that the C-terminal domain is distantly related to MutT, a dNTPase which hydrolyzes 8-oxo-dGTP [Noll et al. (1999) Biochemistry 38, 6374-6379]. We have studied the solution structure of the C-terminal domain of MutY by NMR and find striking similarity with the reported solution structure of MutT. Despite low sequence identity between the two proteins, they have similar secondary structure and topology. The C-terminal domain of MutY is composed of two alpha-helices and five beta-strands. The NOESY data indicate that the protein has two beta-sheets. MutT is also a mixed alpha/beta protein with two helices and two beta-sheets composed of five strands. The secondary structure elements are similarly arranged in the two proteins.
Insights
The C-terminal domain of MutY, an enzyme involved in DNA repair, shares a similar structure to MutT, an enzyme that hydrolyzes 8-oxo-dGTP. This finding reveals structural similarities between DNA repair and nucleotide hydrolysis enzymes.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- MutY from Escherichia coli removes adenine mispaired with 7,8-dihydro-8-oxoguanine (8-oxoG), a DNA lesion from oxidative damage.
- MutY has two domains: N-terminal (p26) for catalysis and C-terminal (p13) for substrate recognition and turnover.
- Sequence analysis suggested a distant relationship between MutY's C-terminal domain and MutT, a dNTPase hydrolyzing 8-oxo-dGTP.
Purpose of the Study:
- To determine the solution structure of the C-terminal domain of MutY.
- To compare the structure of the MutY C-terminal domain with that of MutT.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was used to study the solution structure.
- NOESY data were collected to identify protein-protein interactions and structural features.
- Secondary structure analysis was performed to determine the arrangement of helices and beta-sheets.
Main Results:
- The solution structure of the MutY C-terminal domain was determined.
- Striking structural similarity was observed between the MutY C-terminal domain and MutT.
- Both proteins exhibit similar secondary structures and topology, with two alpha-helices and five beta-strands arranged in two beta-sheets.
- This similarity exists despite low sequence identity between the two proteins.
Conclusions:
- The C-terminal domain of MutY shares a similar structure and topology with MutT.
- This structural similarity suggests potential functional or evolutionary links between DNA repair and nucleotide hydrolysis.
- The findings provide insights into the structural basis of enzyme function in DNA maintenance and nucleotide metabolism.