The Aromatic Amino Acid Hydroxylase Mechanism: A Perspective From Computational Chemistry

This chapter presents the information on the function and structure of the amino acid hydroxylases (AAHs), the objectives is to offer information on the catalytic mechanism operating in these non-heme iron-dependent enzymes. In particular, the chapter focuses on mechanistically relevant information that has emerged from molecular-level computational studies. Special attention is paid to the work in this area, although results are put forward in the context of other contributions in the field. All the existing molecular-level computational studies of the AAH catalytic mechanism support the general two-step mechanism. Although individually such theoretical studies can formally only disprove candidate reaction pathways, the unanimous support for the two-step mechanism, involving several cluster models and QM/MM studies based on different X-ray crystal structures and with different choices made in the model building, is a strong argument in favor of this general mechanism. The unanimous support for the two-step mechanism (involving several cluster models and quantum mechanics / molecular mechanics studies based on different X-ray crystal structures and with different choices made in the model building) is a strong argument in favor of this general mechanism. The combined picture emerging from the computational studies thus represents an important contribution to the field.