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rdf:type |
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lifeskim:mentions |
umls-concept:C0030705,
umls-concept:C0086418,
umls-concept:C0205396,
umls-concept:C0268119,
umls-concept:C0348801,
umls-concept:C0441836,
umls-concept:C0443286,
umls-concept:C0596988,
umls-concept:C0598002,
umls-concept:C0662782,
umls-concept:C1880022,
umls-concept:C2603343
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pubmed:issue |
28
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pubmed:dateCreated |
2003-7-4
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pubmed:abstractText |
Biosynthesis of the molybdenum cofactor involves the initial formation of precursor Z, its subsequent conversion to molybdopterin (MPT) by MPT synthase, and attachment of molybdenum to the dithiolene moiety of MPT. The sulfur used for the formation of the dithiolene group of MPT exists in the form of a thiocarboxylate group at the C terminus of the smaller subunit of MPT synthase. Human MPT synthase contains the MOCS2A and MOCS2B proteins that display homology to the Escherichia coli proteins MoaD and MoaE, respectively. MOCS2A and MOCS2B were purified after heterologous expression in E. coli, and the separately purified subunits readily assemble into a functional MPT synthase tetramer. The rate of conversion of precursor Z to MPT by the human enzyme is slower than that of the eubacterial homologue. To obtain insights into the molecular mechanism leading to human molybdenum cofactor deficiency, site-specific mutations identified in patients showing symptoms of molybdenum cofactor deficiency were generated. Characterization of a V7F substitution in MOCS2A, identified in a patient with an unusual mild form of the disease, showed that the mutation weakens the interaction between MOCS2A and MOCS2B, whereas a MOCS2B-E168K mutation identified in a severely affected patient attenuates binding of precursor Z.
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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/Coenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Molybdenum,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrate Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrate Reductases,
http://linkedlifedata.com/resource/pubmed/chemical/Pteridines,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfurtransferases,
http://linkedlifedata.com/resource/pubmed/chemical/molybdenum cofactor,
http://linkedlifedata.com/resource/pubmed/chemical/molybdopterin synthase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26127-34
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12732628-Amino Acid Sequence,
pubmed-meshheading:12732628-Chromatography,
pubmed-meshheading:12732628-Chromatography, High Pressure Liquid,
pubmed-meshheading:12732628-Circular Dichroism,
pubmed-meshheading:12732628-Cloning, Molecular,
pubmed-meshheading:12732628-Coenzymes,
pubmed-meshheading:12732628-DNA, Complementary,
pubmed-meshheading:12732628-Escherichia coli,
pubmed-meshheading:12732628-Gene Library,
pubmed-meshheading:12732628-Genetic Complementation Test,
pubmed-meshheading:12732628-Humans,
pubmed-meshheading:12732628-Metalloproteins,
pubmed-meshheading:12732628-Molecular Sequence Data,
pubmed-meshheading:12732628-Molybdenum,
pubmed-meshheading:12732628-Mutagenesis, Site-Directed,
pubmed-meshheading:12732628-Mutation,
pubmed-meshheading:12732628-Nitrate Reductase,
pubmed-meshheading:12732628-Nitrate Reductases,
pubmed-meshheading:12732628-Protein Binding,
pubmed-meshheading:12732628-Protein Structure, Tertiary,
pubmed-meshheading:12732628-Pteridines,
pubmed-meshheading:12732628-Sequence Homology, Amino Acid,
pubmed-meshheading:12732628-Sulfurtransferases,
pubmed-meshheading:12732628-Time Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency.
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pubmed:affiliation |
Department of Plant Biology, Technical University Braunschweig, 38023 Braunschweig, Germany.
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pubmed:publicationType |
Journal Article
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