Structural similarities between MutT and the C-terminal domain of MutY.
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.
Volk
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Sealy 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
House
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Thiviyanathan
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Luxon
B A
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Zhang
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Lloyd
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Gorenstein
D G
DG
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D003001:Cloning, Molecular; D045647:DNA Glycosylases; D029968:Escherichia coli Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry*; D011487:Protein Conformation; D011755:Pyrophosphatases; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D011755:Pyrophosphatases; C052211:mutT protein, E coli