TY - JOUR
T1 - Structure, function, and mechanism of proline utilization A (PutA)
AU - Liu, Li Kai
AU - Becker, Donald F.
AU - Tanner, John J.
N1 - Funding Information:
Research reported in this publication was supported by the NIGMS of the National Institutes of Health under award numbers R01GM065546 , R01GM061068 , and P30GM103335 .
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10/15
Y1 - 2017/10/15
N2 - 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).
AB - 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).
KW - Aldehyde dehydrogenase
KW - Enzyme hysteresis
KW - Flavin-dependent reaction
KW - Flavoprotein
KW - Multifunctional enzymes
KW - Protein structure
KW - Substrate channeling
KW - proline catabolism
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U2 - 10.1016/j.abb.2017.07.005
DO - 10.1016/j.abb.2017.07.005
M3 - Review article
C2 - 28712849
AN - SCOPUS:85025439517
SN - 0003-9861
VL - 632
SP - 142
EP - 157
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -