title: Crystal structure of non-redox regulated SSADH from Escherichia coli.
abstract: SSADH is involved in the final step of GABA degradation, converting SSA to succinic acid in the human mitochondrial matrix, and its activity is known to be regulated via 'redox-switch modulation' of the catalytic loop. We present the crystal structure of EcSSADH, revealing that the catalytic loop of EcSSADH, unlike that of human SSADH, does not undergo disulfide bond-mediated structural changes upon changes of environmental redox status. Subsequent redox change experiments using recombinant proteins confirm the non-redox regulation of this protein. Detailed structural analysis shows that a difference in the conformation of the connecting loop (beta15-beta16) causes the formation of a water molecule-mediated hydrogen bond network between the connecting loop and the catalytic loop in EcSSADH, making the catalytic loop of EcSSADH more rigid compared to that of human SSADH. The cytosolic localization of EcSSADH and the cellular function of the GABA shunt in E. coli might result in the non-redox mediated regulatory mechanisms of the protein.
authors.affiliation: Pohang Accelerator Laboratory, Pohang University of Science and Technology, San31, Hyoja-Dong, Nam-Gu, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Ahn
authors.forename: Yeon-Gil
authors.initials: YG
authors.lastname: Kim
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D050644:Succinate-Semialdehyde Dehydrogenase / Q000737:chemistry* / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase; C547505:gabD protein, E coli