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rdf:type |
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lifeskim:mentions |
umls-concept:C0015127,
umls-concept:C0026882,
umls-concept:C0158981,
umls-concept:C0205374,
umls-concept:C0392756,
umls-concept:C1148926,
umls-concept:C1314792,
umls-concept:C1412082,
umls-concept:C1514562,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
7
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pubmed:dateCreated |
2008-7-1
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pubmed:abstractText |
Activating mutations in the pore-forming Kir6.2 (KCNJ11) and regulatory sulphonylurea receptor SUR1 (ABCC8) subunits of the K(ATP) channel are a common cause of transient neonatal diabetes mellitus (TNDM). We identified a new TNDM mutation (R826W) in the first nucleotide-binding domain (NBD1) of SUR1. The mutation was found in a region that heterodimerizes with NBD2 to form catalytic site 2. Functional analysis showed that this mutation decreases MgATP hydrolysis by purified maltose-binding protein MBP-NBD1 fusion proteins. Inhibition of ATP hydrolysis by MgADP or BeF was not changed. The results indicate that the ATPase cycle lingers in the post-hydrolytic MgADP.P(i)-bound state, which is associated with channel activation. The extent of MgADP-dependent activation of K(ATP) channel activity was unaffected by the R826W mutation, but the time course of deactivation was slowed. Channel inhibition by MgATP was reduced, leading to an increase in resting whole-cell currents. In pancreatic beta cells, this would lead to less insulin secretion and thereby diabetes.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-11395395,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-11502255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-15034580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-15893323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-16123337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-16858415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-16885550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-16971936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-17446535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-17485460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-17561960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-17652156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-17723295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-18025464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-4202581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-8650576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-9144288,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-9382893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18497752-9618560
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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/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Inwardly...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptophan,
http://linkedlifedata.com/resource/pubmed/chemical/sulfonylurea receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1469-3178
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
648-54
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18497752-ATP-Binding Cassette Transporters,
pubmed-meshheading:18497752-Adenosine Diphosphate,
pubmed-meshheading:18497752-Adenosine Triphosphatases,
pubmed-meshheading:18497752-Adenosine Triphosphate,
pubmed-meshheading:18497752-Amino Acid Sequence,
pubmed-meshheading:18497752-Amino Acid Substitution,
pubmed-meshheading:18497752-Arginine,
pubmed-meshheading:18497752-Child,
pubmed-meshheading:18497752-Diabetes Mellitus,
pubmed-meshheading:18497752-Humans,
pubmed-meshheading:18497752-Infant, Newborn,
pubmed-meshheading:18497752-Infant, Newborn, Diseases,
pubmed-meshheading:18497752-Ion Channel Gating,
pubmed-meshheading:18497752-Kinetics,
pubmed-meshheading:18497752-Male,
pubmed-meshheading:18497752-Molecular Sequence Data,
pubmed-meshheading:18497752-Mutant Proteins,
pubmed-meshheading:18497752-Mutation,
pubmed-meshheading:18497752-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:18497752-Protein Structure, Secondary,
pubmed-meshheading:18497752-Protein Structure, Tertiary,
pubmed-meshheading:18497752-Receptors, Drug,
pubmed-meshheading:18497752-Tryptophan
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pubmed:year |
2008
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pubmed:articleTitle |
A mutation (R826W) in nucleotide-binding domain 1 of ABCC8 reduces ATPase activity and causes transient neonatal diabetes.
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pubmed:affiliation |
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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