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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1995-5-1
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pubmed:abstractText |
Crystal structures of the DNA repair enzyme human uracil-DNA glycosylase (UDG), combined with mutational analysis, reveal the structural basis for the specificity of the enzyme. Within the classic alpha/beta fold of UDG, sequence-conserved residues form a positively charged, active-site groove the width of duplex DNA, at the C-terminal edge of the central four-stranded parallel beta sheet. In the UDG-6-aminouracil complex, uracil binds at the base of the groove within a rigid preformed pocket that confers selectivity for uracil over other bases by shape complementary and by main chain and Asn-204 side chain hydrogen bonds. Main chain nitrogen atoms are positioned to stabilize the oxyanion intermediate generated by His-268 acting via nucleophilic attack or general base mechanisms. Specific binding of uracil flipped out from a DNA duplex provides a structural mechanism for damaged base recognition.
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pubmed:grant |
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0092-8674
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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 |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
869-78
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7697717-Amino Acid Sequence,
pubmed-meshheading:7697717-Animals,
pubmed-meshheading:7697717-Asparagine,
pubmed-meshheading:7697717-Binding Sites,
pubmed-meshheading:7697717-Catalysis,
pubmed-meshheading:7697717-Cloning, Molecular,
pubmed-meshheading:7697717-Crystallography, X-Ray,
pubmed-meshheading:7697717-DNA Damage,
pubmed-meshheading:7697717-DNA Glycosylases,
pubmed-meshheading:7697717-DNA Mutational Analysis,
pubmed-meshheading:7697717-DNA Repair,
pubmed-meshheading:7697717-Escherichia coli,
pubmed-meshheading:7697717-Histidine,
pubmed-meshheading:7697717-Humans,
pubmed-meshheading:7697717-Hydrogen Bonding,
pubmed-meshheading:7697717-Models, Molecular,
pubmed-meshheading:7697717-Molecular Sequence Data,
pubmed-meshheading:7697717-N-Glycosyl Hydrolases,
pubmed-meshheading:7697717-Protein Biosynthesis,
pubmed-meshheading:7697717-Protein Conformation,
pubmed-meshheading:7697717-Protein Folding,
pubmed-meshheading:7697717-Protein Structure, Secondary,
pubmed-meshheading:7697717-Rabbits,
pubmed-meshheading:7697717-Recombinant Proteins,
pubmed-meshheading:7697717-Reticulocytes,
pubmed-meshheading:7697717-Substrate Specificity,
pubmed-meshheading:7697717-Uracil-DNA Glycosidase
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pubmed:year |
1995
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pubmed:articleTitle |
Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis.
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pubmed:affiliation |
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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