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Structural biology of proline catabolism

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Abstract

The proline catabolic enzymes proline dehydrogenase and Δ1-pyrroline-5-carboxylate dehydrogenase catalyze the 4-electron oxidation of proline to glutamate. These enzymes play important roles in cellular redox control, superoxide generation, apoptosis and cancer. In some bacteria, the two enzymes are fused into the bifunctional enzyme, proline utilization A. Here we review the three-dimensional structural information that is currently available for proline catabolic enzymes. Crystal structures have been determined for bacterial monofunctional proline dehydrogenase and Δ1-pyrroline-5-carboxylate dehydrogenase, as well as the proline dehydrogenase and DNA-binding domains of proline utilization A. Some of the functional insights provided by analyses of these structures are discussed, including substrate recognition, catalytic mechanism, biochemical basis of inherited proline catabolic disorders and DNA recognition by proline utilization A.

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Acknowledgments

I would like to express my sincere gratitude to my former and current students and postdoctoral associates who have contributed to the work reviewed here: Dr. Tommi White, Dr. John Larson, Min Zhang, Dr. Jermaine Jenkins, Dr. Jonathan Schuermann, Dr. Yong-Huan Lee and Shorena Nadaraia. I also thank Prof. Donald Becker and his students for their crucial contributions to this research. Finally, I thank Dr. David Valle for insightful discussions about substrate specificities of human PRODHs. This research was supported by NIH grant GM065546. Part of the research reviewed here was performed at Advanced Light Source beamline 4.2.2. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences Division, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098 at Lawrence Berkeley National Laboratory.

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  1. Departments of Chemistry and Biochemistry, University of Missouri, Columbia, MO, 65211, USA

    John J. Tanner

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Tanner, J.J. Structural biology of proline catabolism. Amino Acids 35, 719–730 (2008). https://doi.org/10.1007/s00726-008-0062-5

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