THE 3-DIMENSIONAL STRUCTURES OF MUTANTS OF PORPHOBILINOGEN DEAMINASE - TOWARD AN UNDERSTANDING OF THE STRUCTURAL BASIS OF ACUTE INTERMITTENT PORPHYRIA

Mutations in the human gene for the enzyme porphobilinogen deaminase g ive rise to an inherited disease of heme biosynthesis, acute intermitt ent porphyria. Knowledge of the 3-dimensional structure of human porph obilinogen deaminase, based on the structure of the bacterial enzyme, allows correlation of structure with gene organization and leads to an understanding of the relationship between mutations in the gene, stru ctural and functional changes of the enzyme, and the symptoms of the d isease. Most mutations occur in exons 10 and 12, often changing amino acids in the active site. Several of these are shown to be involved in binding the primer or substrate; none modifies Asp 84, which is essen tial for catalytic