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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-6-7
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pubmed:abstractText |
The human MTH1 antimutator protein hydrolyzes mutagenic oxidized nucleotides, and thus prevents their incorporation into DNA and any subsequent mutation. We have examined its great selectivity for oxidized nucleotides by analyzing the structure of the protein and its interaction with nucleotides, as reflected in the fluorescence of its tryptophan residues. The binding of nucleotides decreased the intensity of MTH1 protein fluorescence and red-shifted the emission peak, indicating that at least one tryptophan residue is close to the binding site. Oxidized nucleotides (2-OH-dATP and 8-oxo-dGTP) produced a larger decrease in fluorescence intensity than did unoxidized nucleotides, and MTH1 protein had a much higher binding affinity for oxidized nucleotides. Deconvolution of protein fluorescence by comparison of its quenching by positively (Cs(+)) and negatively (I(-)) charged ions indicated that the MTH1 tryptophan residues are in two different environments. One class of tryptophan residues is exposed to solvent but in a negatively charged environment; the other class is partially buried. While the binding of unoxidized nucleotides quenches the fluorescence of only class 1 tryptophan residue(s), the binding of oxidized nucleotides quenched that of class 2 tryptophan residue(s) as well. This suggests that selectivity is due to additional contact between the protein and the oxidized nucleotide. Mutation analysis indicated that the tryptophan residue at position 117, which is in a negative environment, is in contact with nucleotides. The negatively charged residues in the binding site probably correlate with the finding that nucleotide binding requires metal ions and depends upon their nature. Positively charged metal ions probably act by neutralizing the negatively charged nucleotide phosphate groups. (c) 2002 Elsevier Science Ltd.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-hydroxydeoxyadenosine triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/8-oxodGTPase,
http://linkedlifedata.com/resource/pubmed/chemical/8-oxodeoxyguanosine triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Cations, Divalent,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Repair Enzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyguanine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MTH1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptophan
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
319
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
129-39
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12051941-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12051941-Adenosine Triphosphate,
pubmed-meshheading:12051941-Cations, Divalent,
pubmed-meshheading:12051941-DNA Repair Enzymes,
pubmed-meshheading:12051941-Deoxyguanine Nucleotides,
pubmed-meshheading:12051941-Fluorescence Polarization,
pubmed-meshheading:12051941-Fungal Proteins,
pubmed-meshheading:12051941-Humans,
pubmed-meshheading:12051941-Kinetics,
pubmed-meshheading:12051941-Membrane Proteins,
pubmed-meshheading:12051941-Mutagens,
pubmed-meshheading:12051941-Oxidation-Reduction,
pubmed-meshheading:12051941-Phosphoric Monoester Hydrolases,
pubmed-meshheading:12051941-Protein Binding,
pubmed-meshheading:12051941-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:12051941-Spectrometry, Fluorescence,
pubmed-meshheading:12051941-Tryptophan
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pubmed:year |
2002
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pubmed:articleTitle |
Role of tryptophan residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein.
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pubmed:affiliation |
UMR 216, Centre National de la Recherche Scientifique & Institut Curie, 91405 Orsay, France. masa@chimbio.univ-nantes.fr
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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