First insights into structure-function relationships of alkylglycerol monooxygenase

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 journalArticle

Abstract

Alkylglycerol monooxygenase is a tetrahydrobiopterin-dependent enzyme that cleaves the O-alkyl-bond of alkylglycerols. It is an exceptionally unstable, hydrophobic membrane protein which has never been purified in active form. Recently, we were able to identify the sequence of alkylglycerol monooxygenase. TMEM195, the gene coding for alkylglycerol monooxygenase, belongs to the fatty acid hydroxylases, a family of integral membrane enzymes which have an 8-histidine motif crucial for catalysis. Mutation of each of these residues resulted in a complete loss of activity. We now extended the mutational analysis to another 25 residues and identified three further residues conserved throughout all members of the fatty acid hydroxylases which are essential for alkylglycerol monooxygenase activity. Furthermore, mutation of a specific glutamate resulted in an 18-fold decreased affinity of the protein to tetrahydrobiopterin, strongly indicating a potential important role in cofactor interaction. A glutamate residue in a comparable amino acid surrounding had already been shown to be responsible for tetrahydrobiopterin binding in the aromatic amino acid hydroxylases. Ab initio modelling of the enzyme yielded a structural model for the central part of alkylglycerol monooxygenase where all essential residues identified by mutational analysis are in close spatial vicinity, thereby defining the potential catalytic site of this enzyme.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalPteridines
Volume24
Issue number1
DOIs
StatePublished - Jun 2013

Keywords

  • Alkylglycerols
  • Ether lipids
  • Tetrahydrobiopterin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Medicine

Fingerprint Dive into the research topics of 'First insights into structure-function relationships of alkylglycerol monooxygenase'. Together they form a unique fingerprint.

  • Cite this

    Watschinger, K., Fuchs, J. E., Yarov-Yarovoy, V., Keller, M. A., Golderer, G., Hermetter, A., Werner-Felmayer, G., Hulo, N., & Werner, E. R. (2013). First insights into structure-function relationships of alkylglycerol monooxygenase. Pteridines, 24(1), 99-103. https://doi.org/10.1515/pterid-2013-0007