Catalytic residues and a predicted structure of tetrahydrobiopterin- dependent alkylglycerol mono-oxygenase

Katrin Watschinger, Julian E. Fuchs, Vladimir Yarov-Yarovoy, Markus A. Keller, Georg Golderer, Albin Hermetter, Gabriele Werner-Felmayer, Nicolas Hulo, Ernst R. Werner

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Alkylglycerol mono-oxygenase (EC forms a third, distinct, class among tetrahydrobiopterin-dependent enzymes in addition to aromatic amino acid hydroxylases and nitric oxide synthases. Its protein sequence contains the fatty acid hydroxylase motif, a signature indicative of a di-iron centre, which contains eight conserved histidine residues. Membrane enzymes containing this motif, including alkylglycerol mono-oxygenase, are especially labile and so far have not been purified to homogeneity in active form. To obtain a first insight into structure-function relationships of this enzyme, we performed site-directed mutagenesis of 26 selected amino acid residues and expressed wild-type and mutant proteins containing a C-terminal Myc tag together with fatty aldehyde dehydrogenase in Chinese-hamster ovary cells. Among all of the acidic residues within the eight-histidinemotif, onlymutation of Glu 137 to alanine led to an 18-fold increase in the Michaelis-Menten constant for tetrahydrobiopterin, suggesting a role in tetrahydrobiopterin interaction. A ninth additional histidine residue essential for activity was also identified. Nine membrane domains were predicted by four programs: ESKW, TMHMM, MEMSAT and Phobius. Prediction of a part of the structure using the Rosetta membrane ab initio method led to a plausible suggestion for a structure of the catalytic site of alkylglycerol mono-oxygenase.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalBiochemical Journal
Issue number1
StatePublished - Apr 1 2012


  • Alkylglycerol mono-oxygenase
  • Fatty acid hydroxylase motif
  • Phenylalanine hydroxylase
  • Tetrahydrobiopterin
  • Transmembrane domain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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