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Structure of the homodimeric glycine decarboxylase P-protein from Synechocystis sp. PCC 6803 suggests a mechanism for redox regulation.

Hasse D, Andersson E, Carlsson G, Masloboy A, Hagemann M, Bauwe H, Andersson I
J Biol Chem 288 35333-45 (2013)
Related entries: 4lhc, 4lhd

Cited: 19 times
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Abstract

Glycine decarboxylase, or P-protein, is a pyridoxal 5'-phosphate (PLP)-dependent enzyme in one-carbon metabolism of all organisms, in the glycine and serine catabolism of vertebrates, and in the photorespiratory pathway of oxygenic phototrophs. P-protein from the cyanobacterium Synechocystis sp. PCC 6803 is an α2 homodimer with high homology to eukaryotic P-proteins. The crystal structure of the apoenzyme shows the C terminus locked in a closed conformation by a disulfide bond between Cys(972) in the C terminus and Cys(353) located in the active site. The presence of the disulfide bridge isolates the active site from solvent and hinders the binding of PLP and glycine in the active site. Variants produced by substitution of Cys(972) and Cys(353) by Ser using site-directed mutagenesis have distinctly lower specific activities, supporting the crucial role of these highly conserved redox-sensitive amino acid residues for P-protein activity. Reduction of the 353-972 disulfide releases the C terminus and allows access to the active site. PLP and the substrate glycine bind in the active site of this reduced enzyme and appear to cause further conformational changes involving a flexible surface loop. The observation of the disulfide bond that acts to stabilize the closed form suggests a molecular mechanism for the redox-dependent activation of glycine decarboxylase observed earlier.

Articles - 4lgl mentioned but not cited (2)

  1. Structure of the homodimeric glycine decarboxylase P-protein from Synechocystis sp. PCC 6803 suggests a mechanism for redox regulation. Hasse D, Andersson E, Carlsson G, Masloboy A, Hagemann M, Bauwe H, Andersson I. J Biol Chem 288 35333-35345 (2013)
  2. Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. Nematollahi A, Sun G, Harrop SJ, Hanrahan JR, Church WB. Int J Mol Sci 17 446 (2016)


Reviews citing this publication (2)

  1. The redox control of photorespiration: from biochemical and physiological aspects to biotechnological considerations. Keech O, Gardeström P, Kleczkowski LA, Rouhier N. Plant Cell Environ 40 553-569 (2017)
  2. Understanding and Engineering Glycine Cleavage System and Related Metabolic Pathways for C1-Based Biosynthesis. Ren J, Wang W, Nie J, Yuan W, Zeng AP. Adv Biochem Eng Biotechnol 180 273-298 (2022)

Articles citing this publication (15)

  1. The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. Coughlin CR, Swanson MA, Kronquist K, Acquaviva C, Hutchin T, Rodríguez-Pombo P, Väisänen ML, Spector E, Creadon-Swindell G, Brás-Goldberg AM, Rahikkala E, Moilanen JS, Mahieu V, Matthijs G, Bravo-Alonso I, Pérez-Cerdá C, Ugarte M, Vianey-Saban C, Scharer GH, Van Hove JL. Genet Med 19 104-111 (2017)
  2. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia. Swanson MA, Coughlin CR, Scharer GH, Szerlong HJ, Bjoraker KJ, Spector EB, Creadon-Swindell G, Mahieu V, Matthijs G, Hennermann JB, Applegarth DA, Toone JR, Tong S, Williams K, Van Hove JL. Ann Neurol 78 606-618 (2015)
  3. Redox-Regulation of Photorespiration through Mitochondrial Thioredoxin o1. Reinholdt O, Schwab S, Zhang Y, Reichheld JP, Fernie AR, Hagemann M, Timm S. Plant Physiol 181 442-457 (2019)
  4. Discovery of a sesamin-metabolizing microorganism and a new enzyme. Kumano T, Fujiki E, Hashimoto Y, Kobayashi M. Proc Natl Acad Sci U S A 113 9087-9092 (2016)
  5. Identification of a RAI1-associated disease network through integration of exome sequencing, transcriptomics, and 3D genomics. Loviglio MN, Beck CR, White JJ, Leleu M, Harel T, Guex N, Niknejad A, Bi W, Chen ES, Crespo I, Yan J, Charng WL, Gu S, Fang P, Coban-Akdemir Z, Shaw CA, Jhangiani SN, Muzny DM, Gibbs RA, Rougemont J, Xenarios I, Lupski JR, Reymond A. Genome Med 8 105 (2016)
  6. Biocomputational Analyses and Experimental Validation Identify the Regulon Controlled by the Redox-Responsive Transcription Factor RpaB. Riediger M, Kadowaki T, Nagayama R, Georg J, Hihara Y, Hess WR. iScience 15 316-331 (2019)
  7. Nonketotic hyperglycinemia: Functional assessment of missense variants in GLDC to understand phenotypes of the disease. Bravo-Alonso I, Navarrete R, Arribas-Carreira L, Perona A, Abia D, Couce ML, García-Cazorla A, Morais A, Domingo R, Ramos MA, Swanson MA, Van Hove JLK, Ugarte M, Pérez B, Pérez-Cerdá C, Rodríguez-Pombo P. Hum Mutat 38 678-691 (2017)
  8. mTORC1 activity regulates post-translational modifications of glycine decarboxylase to modulate glycine metabolism and tumorigenesis. Liu R, Zeng LW, Gong R, Yuan F, Shu HB, Li S. Nat Commun 12 4227 (2021)
  9. A Shortest-Path-Based Method for the Analysis and Prediction of Fruit-Related Genes in Arabidopsis thaliana. Zhu L, Zhang YH, Su F, Chen L, Huang T, Cai YD. PLoS One 11 e0159519 (2016)
  10. Large scale analyses of genotype-phenotype relationships of glycine decarboxylase mutations and neurological disease severity. Farris J, Calhoun B, Alam MS, Lee S, Haldar K. PLoS Comput Biol 16 e1007871 (2020)
  11. The role of conserved Cys residues in Brassica rapa auxin amidohydrolase: Cys139 is crucial for the enzyme activity and Cys320 regulates enzyme stability. Smolko A, Šupljika F, Martinčić J, Jajčanin-Jozić N, Grabar-Branilović M, Tomić S, Ludwig-Müller J, Piantanida I, Salopek-Sondi B. Phys Chem Chem Phys 18 8890-8900 (2016)
  12. Genomic analyses of glycine decarboxylase neurogenic mutations yield a large-scale prediction model for prenatal disease. Farris J, Alam MS, Rajashekara AM, Haldar K. PLoS Genet 17 e1009307 (2021)
  13. Improvement of glycine biosynthesis from one-carbon compounds and ammonia catalyzed by the glycine cleavage system in vitro. Xu Y, Ren J, Wang W, Zeng AP. Eng Life Sci 22 40-53 (2022)
  14. Pathogenic variants in GCSH encoding the moonlighting H-protein cause combined nonketotic hyperglycinemia and lipoate deficiency. Arribas-Carreira L, Dallabona C, Swanson MA, Farris J, Østergaard E, Tsiakas K, Hempel M, Aquaviva-Bourdain C, Koutsoukos S, Stence NV, Magistrati M, Spector EB, Kronquist K, Christensen M, Karstensen HG, Feichtinger RG, Achleitner MT, Lawrence Merritt Ii J, Pérez B, Ugarte M, Grünewald S, Riela AR, Julve N, Arnoux JB, Haldar K, Donnini C, Santer R, Lund AM, Mayr JA, Rodriguez-Pombo P, Van Hove JLK. Hum Mol Genet 32 917-933 (2023)
  15. Turn air-captured CO2 with methanol into amino acid and pyruvate in an ATP/NAD(P)H-free chemoenzymatic system. Liu J, Zhang H, Xu Y, Meng H, Zeng AP. Nat Commun 14 2772 (2023)


Related citations provided by authors (1)

  1. Crystallization and preliminary X-ray diffraction analyses of the homodimeric glycine decarboxylase (P-protein) from the cyanobacterium Synechocystis sp. PCC 6803.. Hasse D, Hagemann M, Andersson I, Bauwe H Acta Crystallogr Sect F Struct Biol Cryst Commun 66 187-91 (2010)

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