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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 |
2004-7-27
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pubmed:abstractText |
GDP-mannose glycosyl hydrolase (GDPMH) catalyzes the hydrolysis of GDP-mannose and GDP-glucose to GDP and sugar by substitution with inversion at C1 of the sugar. The enzyme has a modified Nudix motif and requires one divalent cation for activity. The 1.3 A X-ray structure of the GDPMH-Mg(2+)-GDP complex, together with kinetic, mutational, and NMR data, suggests a mechanism for the GDPMH reaction. Several residues and the divalent cation strongly promote the departure of the GDP leaving group, supporting a dissociative mechanism. Comparison of the GDPMH structure with that of a typical Nudix hydrolase suggests how sequence changes result in the switch of catalytic activity from P-O bond cleavage to C-O bond cleavage. Changes in the Nudix motif result in loss of binding of at least one Mg(2+) ion, and shortening of a loop by 6 residues shifts the catalytic base by approximately 10 A.
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pubmed:grant |
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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 |
Jun
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pubmed:issn |
0969-2126
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
927-35
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15274914-Amino Acid Motifs,
pubmed-meshheading:15274914-Amino Acid Sequence,
pubmed-meshheading:15274914-Binding Sites,
pubmed-meshheading:15274914-Carbon,
pubmed-meshheading:15274914-Catalysis,
pubmed-meshheading:15274914-Cations,
pubmed-meshheading:15274914-Crystallography, X-Ray,
pubmed-meshheading:15274914-Dimerization,
pubmed-meshheading:15274914-Escherichia coli,
pubmed-meshheading:15274914-Guanosine Diphosphate,
pubmed-meshheading:15274914-Guanosine Diphosphate Mannose,
pubmed-meshheading:15274914-Hydrolysis,
pubmed-meshheading:15274914-Ions,
pubmed-meshheading:15274914-Kinetics,
pubmed-meshheading:15274914-Magnesium,
pubmed-meshheading:15274914-Magnetic Resonance Spectroscopy,
pubmed-meshheading:15274914-Mannose,
pubmed-meshheading:15274914-Models, Molecular,
pubmed-meshheading:15274914-Molecular Sequence Data,
pubmed-meshheading:15274914-Mutation,
pubmed-meshheading:15274914-N-Glycosyl Hydrolases,
pubmed-meshheading:15274914-Phosphorus,
pubmed-meshheading:15274914-Protein Binding,
pubmed-meshheading:15274914-Protein Conformation,
pubmed-meshheading:15274914-Protein Structure, Secondary,
pubmed-meshheading:15274914-Protein Structure, Tertiary,
pubmed-meshheading:15274914-Sequence Homology, Amino Acid,
pubmed-meshheading:15274914-Structure-Activity Relationship
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pubmed:year |
2004
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pubmed:articleTitle |
Structure and mechanism of GDP-mannose glycosyl hydrolase, a Nudix enzyme that cleaves at carbon instead of phosphorus.
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pubmed:affiliation |
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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