Structure of catalase-A from Saccharomyces cerevisiae

The structure of the peroxisomal catalase A from the budding yeast Saccharo myces cerevisiae, with 515 residues per subunit, has been determined and re fined to 2.4 Angstrom resolution. The crystallographic agreement factors R and R-free are 15.4% and 19.8%, respectively. A tetramer with accurate 222- molecular symmetry is located in the asymmetric unit of the crystal. The co nformation of the central core of catalase A, about 300 residues, remains s imilar to the structure of catalases from distantly related organisms. In c ontrast; catalase A lacks a carboxy-terminal domain equivalent to that foun d in catalase from Penicillium vitalae, the only other fungal catalase stru cture available. Structural peculiarities related with the heme and NADP(H) binding pockets can be correlated with biochemical characteristics of the catalase A enzyme. The network of molecular cavities and channels, filled w ith solvent molecules, supports the existence of one major substrate entry and at least two possible alternative pathways to the heme active site. The structure of the variant protein Val111Ala, also determined by X-ray cryst allography at 2.8 Angstrom resolution, shows a few, well-localized, differe nces with respect to the wild-type enzyme. These differences, that include the widening of the entry channel in its narrowest point, provide an explan ation for both the increased peroxidatic activity and the reduced catalatic activity of this mutant. (C) 1999 Academic Press.