Untersuchungen zur molekularen Ursache der Multiplen Sulfatase-Defizienz: Reinigung, Funktions- und Strukturanalyse von varianten Proteinen des Formylglycin-generierenden Enzyms

The molecular cause of multiple sulfatase deficiency: cleaning, functional and structural analysis of variant proteins of formylglycine-generating enzyme

by Helene Mühlhausen
Doctoral thesis
Date of Examination:2015-01-14
Date of issue:2014-12-05
Advisor:Prof. Dr. Peter Rehling
Referee:Prof. Dr. Margarete Schön
Referee:Prof. Dr. Markus Zweckstetter
Persistent Address: http://dx.doi.org/10.53846/goediss-4808

 

 

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Abstract

English

The Multiple sulfatase deficiency (MSD) is an inherited metabolic disease caused by mutations in the SUMF1 gene. The encoded ER-located Cα-formylglycine-generating enzyme (FGE) catalyzes the activation of newly synthesized sulfatases by cotranslationally oxidizing a conserved cysteine residue to the Cα-formylglycine (FGly), the catalytically active amino acid residue of sulfatases. Some FGE mutants have already been characterized biochemically and initial assumptions about the relationship between genotype and phenotype of the disease are set up. Crystallization of the FGE-WT enabled - about the localization of the mutations in the model - to make predictions in terms of their expected damage. The confirmation of the suspected relationship between genotypic and phenotypic specificities effects, using the crystal structure model of a FGE mutant could not be achieved to date. Currently no data from completely purified FGE mutants exists.
Keywords: FGE; mutants; purification; substrate binding; crystal structure; multiple sulfatase deficiency; formylglycine generating enzyme; affinity chromatography; variant proteins
Schlagwörter: Formylglycin generierendes Enzym; Multiple Sulfatase Defizienz; Aufreinigung; Mutanten; Affinitätschromatographie; Anionenaustauschchromatographie; Substratbindung; Kristallstruktur
 
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