Kinetic and structural characterization for cofactor preference of succinic semialdehyde dehydrogenase from Streptococcus pyogenes

Eun H yuk Jang, Seong A h Park, Young Min Chi, Ki S eog Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The γ-Aminobutyric acid (GABA) that is found in prokaryotic and eukaryotic organisms has been used in various ways as a signaling molecule or a significant component generating metabolic energy under conditions of nutrient limitation or stress, through GABA catabolism. Succinic semialdehyde dehydrogenase (SSADH) catalyzes the oxidation of succinic semialdehyde to succinic acid in the final step of GABA catabolism. Here, we report the catalytic properties and two crystal structures of SSADH from Streptococcus pyogenes (SpSSADH) regarding its cofactor preference. Kinetic analysis showed that SpSSADH prefers NADP(+) over NAD(+) as a hydride acceptor. Moreover, the structures of SpSSADH were determined in an apo-form and in a binary complex with NADP(+) at 1.6 Å and 2.1 Å resolutions, respectively. Both structures of SpSSADH showed dimeric conformation, containing a single cysteine residue in the catalytic loop of each subunit. Further structural analysis and sequence comparison of SpSSADH with other SSADHs revealed that Ser158 and Tyr188 in SpSSADH participate in the stabilization of the 2'-phosphate group of adenine-side ribose in NADP(+). Our results provide structural insights into the cofactor preference of SpSSADH as the gram-positive bacterial SSADH.

Original languageEnglish
Pages (from-to)719-726
Number of pages8
JournalMolecules and Cells
Volume37
Issue number10
DOIs
Publication statusPublished - 2014 Oct 31

Fingerprint

Succinate-Semialdehyde Dehydrogenase
Streptococcus pyogenes
NADP
gamma-Aminobutyric Acid
Aminobutyrates
Ribose
Succinic Acid
Adenine
NAD
Cysteine
Sequence Analysis
Phosphates
Food

Keywords

  • cofactor preference
  • GabD
  • Streptococcus pyogenes
  • succinic semialdehyde dehydrogenase
  • γ-aminobutyric acid (GABA) catabolism

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kinetic and structural characterization for cofactor preference of succinic semialdehyde dehydrogenase from Streptococcus pyogenes. / Jang, Eun H yuk; Park, Seong A h; Chi, Young Min; Lee, Ki S eog.

In: Molecules and Cells, Vol. 37, No. 10, 31.10.2014, p. 719-726.

Research output: Contribution to journalArticle

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