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The histidin-loop is essential for transport activity of human MDR3: a novel mutation of MDR3 in a patient with progressive familial intrahepatic cholestasis type 3

Experimental evidence has been provided that a histidine-loop within the nucleotide binding domain of ABC transporter is essential for efficient function of this class of transporter proteins. Here we report the first patient with a mutation of the putative histidine‐loop of a human ABC transporter,...

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Hauptverfasser: Dzagania, Tamar (VerfasserIn) , Engelmann, Guido (VerfasserIn) , Flechtenmacher, Christa (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 3 July 2012
In: Gene
Year: 2012, Jahrgang: 506, Heft: 1, Pages: 141-145
ISSN:1879-0038
DOI:10.1016/j.gene.2012.06.029
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Verfasserangaben:Tamar Dzagania, Guido Engelmann, Dieter Häussinger, Lutz Schmitt, Christa Flechtenmacher, Irakli Rtskhiladze, Ralf Kubitz
Beschreibung
Zusammenfassung:Experimental evidence has been provided that a histidine-loop within the nucleotide binding domain of ABC transporter is essential for efficient function of this class of transporter proteins. Here we report the first patient with a mutation of the putative histidine‐loop of a human ABC transporter, the multi drug resistance protein 3 (MDR3). The patient presented at the age of 4years with a history of severe pruritus, elevated serum gamma-glutamyltransferase and bile acid levels since several years suggesting the diagnosis of progressive familial intrahepatic cholestasis type 3 (PFIC-3) due to defects in MDR3. Liver biopsy demonstrated an apparently normal MDR3 expression, however, genetic analysis revealed a novel homozygous mutation in the ABCB4 gene (c.3691C>T) in the patient. This mutation was associated with a change of histidine to tyrosine at amino acid position 1231 of MDR3 (p.H1231Y). As shown by sequence alignment, this amino acid corresponds to the highly conserved histidine of the “H-loop”, which is critical for ATP-hydrolysis, suggesting an essential role of histidine 1231 of human MDR3.
Beschreibung:Gesehen am 15.04.2019
Beschreibung:Online Resource
ISSN:1879-0038
DOI:10.1016/j.gene.2012.06.029

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