Structure of the proline dehydrogenase domain of the multifunctional PutA flavoprotein

Yong Hwan Lee, Shorena Nadaraia, Dan Gu, Donald F Becker, John J. Tanner

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The PutA flavoprotein from Escherichia coli plays multiple roles in proline catabolism by functioning as a membrane-associated bi-functional enzyme and a transcriptional repressor of proline utilization genes. The human homolog of the PutA proline dehydrogenase (PRODH) domain is critical in p53-mediated apoptosis and schizophrenia. Here we report the crystal structure of a 669-residue truncated form of PutA that shows both PRODH and DNA-binding activities, representing the first structure of a PutA protein and a PRODH enzyme from any organism. The structure is a domain-swapped dimer with each subunit comprising three domains: a helical dimerization arm, a 120-residue domain containing a three-helix bundle similar to that in the helix-turn-helix superfamily of DNA-binding proteins and a β/α-barrel PRODH domain with a bound lactate inhibitor. Analysis of the structure provides insight into the mechanism of proline oxidation to pyrroline-5-carboxylate, and functional studies of a mutant protein suggest that the DNA-binding domain is located within the N-terminal 261 residues of E. coli PutA.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalNature Structural Biology
Volume10
Issue number2
DOIs
StatePublished - Feb 1 2003

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Proline Oxidase
Flavoproteins
Proline
Escherichia coli
Dimerization
DNA
DNA-Binding Proteins
Mutant Proteins
Enzymes
Dimers
Lactic Acid
Schizophrenia
Genes
Crystal structure
Apoptosis
Membranes
Oxidation
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

Cite this

Structure of the proline dehydrogenase domain of the multifunctional PutA flavoprotein. / Lee, Yong Hwan; Nadaraia, Shorena; Gu, Dan; Becker, Donald F; Tanner, John J.

In: Nature Structural Biology, Vol. 10, No. 2, 01.02.2003, p. 109-114.

Research output: Contribution to journalArticle

Lee, Yong Hwan ; Nadaraia, Shorena ; Gu, Dan ; Becker, Donald F ; Tanner, John J. / Structure of the proline dehydrogenase domain of the multifunctional PutA flavoprotein. In: Nature Structural Biology. 2003 ; Vol. 10, No. 2. pp. 109-114.
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