ABSTRACT Human ornithine aminotransferase (hOAT) is a mitochondrial matrix pyridoxal‐5′‐phosphate enzyme (PLP) that catalyzes the reversible transfer of the δ‐amino group of L‐ornithine (L‐Orn) to α‐ketoglutarate (α‐KG) yielding glutamate‐5‐semialdehyde (GSA) and glutamate. GSA is prone to cyclize to Δ1‐pyrroline‐5‐carboxylate. Human OAT holds significant clinical and scientific interest because (i) its dysfunction causes gyrate atrophy (GA) of the choroid and retina, a rare autosomal recessive disease, and (ii) it is recognized as a potential target for chemotherapeutic drug development, being overexpressed in some types of cancer. Here, we review the kinetic and structural features of the enzyme, as well as the mechanistic aspects of hOAT inhibition. Moreover, we focus our attention on the characterization of the structural and functional properties of the artificial variants and of those associated with GA. Considering that great progress toward the characterization of the pathogenic variants has been reached in the last few years, we summarize here, by revisiting the data available on the hOAT and its variants as purified recombinant form, the current understanding of (i) the molecular defect(s) of studied disease‐causing mutations and (ii) the residues (particularly, active site residues critical for dictating the reaction specificity) and/or regions of the enzyme crucial for its folding and/or catalytic properties.
Floriani et al. (Thu,) studied this question.