S-Adenosylhomocysteine hydrolase (AdoHcyase) deficiency: enzymatic capabilities of human AdoHcyase are highly effected by changes to codon 89 and its surrounding residues

Biochemical and Biophysical Research Communications
Robert BeluzićOliver Vugrek

Abstract

Recently, S-adenosylhomocysteine hydrolase deficiency was confirmed for the first time in an adult. Two missense mutations in codons 89 (A>V) and 143 (Y>C) in the AdoHcyase gene were identified [N.R.M. Buist, B. Glenn, O. Vugrek, C. Wagner, S. Stabler, R.H. Allen, I. Pogribny, A. Schulze, S.H. Zeisel, I. Barić, S.H. Mudd, S-Adenosylhomocysteine hydrolase deficiency in a 26-year-old man, J. Inh. Metab. Dis. 29 (2006) 538-545]. Accordingly, we have proven the Y143C mutation to be highly inactivating [R. Beluzić, M. Cuk, T. Pavkov, K. Fumić, I. Barić, S.H. Mudd, I. Jurak, O. Vugrek, A single mutation at tyrosine 143 of human S-adenosylhomocysteine hydrolase renders the enzyme thermosensitive and effects the oxidation state of bound co-factor NAD, Biochem. J. 400 (2006) 245-253]. Now we report that the A89V exchange leads to a 70% loss of enzymatic activity, respectively. Circular dichroism analysis of recombinant p.A89V protein shows a significantly reduced unfolding temperature by 5.5 degrees C compared to wild-type. Gel filtration of mutant protein is almost identical to wild-type indicating assembly of subunits into the tetrameric complex. However, electrophoretic mobility of p.A89V is notably faster as shown by native polyacry...Continue Reading

References

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Jul 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R J HohmanM Veron
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Aug 3, 2005·The International Journal of Biochemistry & Cell Biology·Taro YamadaFusao Takusagawa
Jun 1, 2006·Journal of Inherited Metabolic Disease·N R M BuistS H Mudd
Dec 14, 2006·European Journal of Human Genetics : EJHG·Ksenija FumićOliver Vugrek

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Citations

Jul 9, 2009·Journal of Inherited Metabolic Disease·Ivo Barić
Nov 4, 2015·Molecular Genetics and Metabolism·Stefan StenderHelen H Hobbs
Feb 11, 2011·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·S Harvey Mudd
Jun 7, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Benoit DevogelaereHumbert De Smedt
Jul 22, 2020·Ophthalmic Genetics·Monika K Grudzinska PechhackerElise Hèon

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