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

'Bioinformatics' analysis indicates that Val89 collides with Thr84 causing sterical incompatibility. Performing site-directed mutagenesis changing Thr84 to 'smaller' Ser84 but preserving similar physico-chemical properties restores most of the catalytic capabilities of the mutant p.A89V enzyme. On the other hand, substitution of Thr84 with Lys84 or Gln84, thereby introducing residues with higher volume in proximity to Ala89 results in inactivation of wild-type protein. In view of our mutational analysis, we consider changes in charge and the sterical incompatibility in mutant p.A89V protein as main reason for enzyme malfunction with AdoHcyase deficiency as consequence.