We study the structural biology of enzymes. We apply this perspective to understand proline metabolism, substrate channeling, the aldehyde dehydrogenase superfamily, inherited metabolic disorders, domains of unknown function (DUFs), and flavoenzymes. We use structural approaches to discover chemical probes for cancer therapy and infectious diseases. Our experimental approaches include X-ray crystallography, small-angle X-ray scattering, electron microscopy, enzyme kinetics, analytical ultracentrifugation, fluorescence thermal shift, and site-directed mutagenesis.