Structure, function, and mechanism of proline utilization A (PutA)

Li Kai Liu, Donald F. Becker, John J. Tanner

Research output: Contribution to journalReview article

26 Scopus citations

Abstract

Proline has important roles in multiple biological processes such as cellular bioenergetics, cell growth, oxidative and osmotic stress response, protein folding and stability, and redox signaling. The proline catabolic pathway, which forms glutamate, enables organisms to utilize proline as a carbon, nitrogen, and energy source. FAD-dependent proline dehydrogenase (PRODH) and NAD+-dependent glutamate semialdehyde dehydrogenase (GSALDH) convert proline to glutamate in two sequential oxidative steps. Depletion of PRODH and GSALDH in humans leads to hyperprolinemia, which is associated with mental disorders such as schizophrenia. Also, some pathogens require proline catabolism for virulence. A unique aspect of proline catabolism is the multifunctional proline utilization A (PutA) enzyme found in Gram-negative bacteria. PutA is a large (>1000 residues) bifunctional enzyme that combines PRODH and GSALDH activities into one polypeptide chain. In addition, some PutAs function as a DNA-binding transcriptional repressor of proline utilization genes. This review describes several attributes of PutA that make it a remarkable flavoenzyme: (1) diversity of oligomeric state and quaternary structure; (2) substrate channeling and enzyme hysteresis; (3) DNA-binding activity and transcriptional repressor function; and (4) flavin redox dependent changes in subcellular location and function in response to proline (functional switching).

Original languageEnglish (US)
Pages (from-to)142-157
Number of pages16
JournalArchives of Biochemistry and Biophysics
Volume632
DOIs
StatePublished - Oct 15 2017

Keywords

  • Aldehyde dehydrogenase
  • Enzyme hysteresis
  • Flavin-dependent reaction
  • Flavoprotein
  • Multifunctional enzymes
  • Protein structure
  • Substrate channeling
  • proline catabolism

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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