2okk Citations

GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop.

Abstract

Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65 and GAD67). GAD67 is constitutively active and is responsible for basal GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is transiently activated in response to the demand for extra GABA in neurotransmission, and cycles between an active holo form and an inactive apo form. We have determined the crystal structures of N-terminal truncations of both GAD isoforms. The structure of GAD67 shows a tethered loop covering the active site, providing a catalytic environment that sustains GABA production. In contrast, the same catalytic loop is inherently mobile in GAD65. Kinetic studies suggest that mobility in the catalytic loop promotes a side reaction that results in cofactor release and GAD65 autoinactivation. These data reveal the molecular basis for regulation of GABA homeostasis.

Articles - 2okk mentioned but not cited (12)

  1. Exploring the role of Mycobacterium avium subspecies paratuberculosis in the pathogenesis of type 1 diabetes mellitus: a pilot study. Naser SA, Thanigachalam S, Dow CT, Collins MT. Gut Pathog 5 14 (2013)
  2. A conserved mechanism of GABA binding and antagonism is revealed by structure-function analysis of the periplasmic binding protein Atu2422 in Agrobacterium tumefaciens. Planamente S, Vigouroux A, Mondy S, Nicaise M, Faure D, Moréra S. J Biol Chem 285 30294-30303 (2010)
  3. Inhibition of glutamate decarboxylase (GAD) by ethyl ketopentenoate (EKP) induces treatment-resistant epileptic seizures in zebrafish. Zhang Y, Vanmeert M, Siekierska A, Ny A, John J, Callewaert G, Lescrinier E, Dehaen W, de Witte PAM, Kaminski RM. Sci Rep 7 7195 (2017)
  4. A generic approach to evaluate how B-cell epitopes are surface-exposed on protein structures. Lollier V, Denery-Papini S, Larré C, Tessier D. Mol Immunol 48 577-585 (2011)
  5. GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production. Mahootchi E, Cannon Homaei S, Kleppe R, Winge I, Hegvik TA, Megias-Perez R, Totland C, Mogavero F, Baumann A, Glennon JC, Miletic H, Kursula P, Haavik J. Sci Adv 6 eabb3713 (2020)
  6. Type I pyridoxal 5'-phosphate dependent enzymatic domains embedded within multimodular nonribosomal peptide synthetase and polyketide synthase assembly lines. Milano T, Paiardini A, Grgurina I, Pascarella S. BMC Struct Biol 13 26 (2013)
  7. Fine Mapping of Glutamate Decarboxylase 65 Epitopes Reveals Dependency on Hydrophobic Amino Acids for Specific Interactions. Valdarnini N, Holm B, Hansen P, Rovero P, Houen G, Trier N. Int J Mol Sci 20 E2909 (2019)
  8. Glutamic acid decarboxylase-derived epitopes with specific domains expand CD4(+)CD25(+) regulatory T cells. Chen G, Han G, Feng J, Wang J, Wang R, Xu R, Shen B, Qian J, Li Y. PLoS One 4 e7034 (2009)
  9. In planta fitness-cost of the Atu4232-regulon encoding for a selective GABA-binding sensor in Agrobacterium. Planamente S, Moréra S, Faure D. Commun Integr Biol 6 e23692 (2013)
  10. PEPOP 2.0: new approaches to mimic non-continuous epitopes. Demolombe V, de Brevern AG, Felicori L, NGuyen C, Machado de Avila RA, Valera L, Jardin-Watelet B, Lavigne G, Lebreton A, Molina F, Moreau V. BMC Bioinformatics 20 387 (2019)
  11. Structure of the mouse acidic amino acid decarboxylase GADL1. Raasakka A, Mahootchi E, Winge I, Luan W, Kursula P, Haavik J. Acta Crystallogr F Struct Biol Commun 74 65-73 (2018)
  12. A Combined Network Pharmacology and Molecular Docking Approach to Investigate Candidate Active Components and Multitarget Mechanisms of Hemerocallis Flowers on Antidepressant Effect. Ma T, Sun Y, Jiang C, Xiong W, Yan T, Wu B, Jia Y. Evid Based Complement Alternat Med 2021 7127129 (2021)


Reviews citing this publication (29)

  1. Development of GABA innervation in the cerebral and cerebellar cortices. Huang ZJ, Di Cristo G, Ango F. Nat Rev Neurosci 8 673-686 (2007)
  2. Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives. Deidda G, Bozarth IF, Cancedda L. Front Cell Neurosci 8 119 (2014)
  3. Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias. Mitoma H, Adhikari K, Aeschlimann D, Chattopadhyay P, Hadjivassiliou M, Hampe CS, Honnorat J, Joubert B, Kakei S, Lee J, Manto M, Matsunaga A, Mizusawa H, Nanri K, Shanmugarajah P, Yoneda M, Yuki N. Cerebellum 15 213-232 (2016)
  4. γ-Aminobutyric acid (GABA) signalling in plants. Ramesh SA, Tyerman SD, Gilliham M, Xu B. Cell Mol Life Sci 74 1577-1603 (2017)
  5. A novel mechanism for GABA synthesis and packaging into synaptic vesicles. Buddhala C, Hsu CC, Wu JY. Neurochem Int 55 9-12 (2009)
  6. Independent origins of neurons and synapses: insights from ctenophores. Moroz LL, Kohn AB. Philos Trans R Soc Lond B Biol Sci 371 20150041 (2016)
  7. Post-translational regulation of L-glutamic acid decarboxylase in the brain. Wei J, Wu JY. Neurochem Res 33 1459-1465 (2008)
  8. Comparative evaluation of recombinant protein production in different biofactories: the green perspective. Merlin M, Gecchele E, Capaldi S, Pezzotti M, Avesani L. Biomed Res Int 2014 136419 (2014)
  9. Exploring the dominant role of Cav1 channels in signalling to the nucleus. Ma H, Cohen S, Li B, Tsien RW. Biosci Rep 33 97-101 (2012)
  10. Islet Autoantibodies. Lampasona V, Liberati D. Curr Diab Rep 16 53 (2016)
  11. Mammalian Dopa decarboxylase: structure, catalytic activity and inhibition. Bertoldi M. Arch Biochem Biophys 546 1-7 (2014)
  12. New insights into brain glutaminases: beyond their role on glutamatergic transmission. Márquez J, Tosina M, de la Rosa V, Segura JA, Alonso FJ, Matés JM, Campos-Sandoval JA. Neurochem Int 55 64-70 (2009)
  13. Trans-Golgi proteins participate in the control of lipid droplet and chylomicron formation. Hesse D, Jaschke A, Chung B, Schürmann A. Biosci Rep 33 1-9 (2013)
  14. GABA(A) receptor and glycine receptor activation by paracrine/autocrine release of endogenous agonists: more than a simple communication pathway. Le-Corronc H, Rigo JM, Branchereau P, Legendre P. Mol Neurobiol 44 28-52 (2011)
  15. Structural biology of the GAD autoantigen. Fenalti G, Buckle AM. Autoimmun Rev 9 148-152 (2010)
  16. Evolutionarily conserved antigens in autoimmune disease: implications for an infective aetiology. Wegner N, Wait R, Venables PJ. Int J Biochem Cell Biol 41 390-397 (2009)
  17. Autoimmunity since the 1957 clonal selection theory: a little acorn to a large oak. Mackay IR. Immunol Cell Biol 86 67-71 (2008)
  18. [11C]Carbon monoxide: advances in production and application to PET radiotracer development over the past 15 years. Taddei C, Pike VW. EJNMMI Radiopharm Chem 4 25 (2019)
  19. GAD antibody-spectrum disorders: progress in clinical phenotypes, immunopathogenesis and therapeutic interventions. Tsiortou P, Alexopoulos H, Dalakas MC. Ther Adv Neurol Disord 14 17562864211003486 (2021)
  20. Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies. Dalakas MC. Neurotherapeutics 19 832-847 (2022)
  21. Structural features of mammalian histidine decarboxylase reveal the basis for specific inhibition. Moya-García AA, Pino-Angeles A, Gil-Redondo R, Morreale A, Sánchez-Jiménez F. Br J Pharmacol 157 4-13 (2009)
  22. Immunobiology of stiff-person syndrome. Raju R, Hampe CS. Int Rev Immunol 27 79-92 (2008)
  23. The role of GABA in islet function. Hagan DW, Ferreira SM, Santos GJ, Phelps EA. Front Endocrinol (Lausanne) 13 972115 (2022)
  24. Genetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies. Guerin AA, Nestler EJ, Berk M, Lawrence AJ, Rossell SL, Kim JH. Neurosci Biobehav Rev 120 48-74 (2021)
  25. Recent progress in studies of factors that elicit pancreatic β-cell expansion. Li Q, Lai ZC. Protein Cell 6 81-87 (2015)
  26. The adjustment of γ-aminobutyric acidA tonic subunits in Huntington's disease: from transcription to translation to synaptic levels into the neostriatum. Rosas-Arellano A, Estrada-Mondragón A, Mantellero CA, Tejeda-Guzmán C, Castro MA. Neural Regen Res 13 584-590 (2018)
  27. Structural Basis for Allostery in PLP-dependent Enzymes. Tran JU, Brown BL. Front Mol Biosci 9 884281 (2022)
  28. Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications. Han SW, Shin JS. Appl Microbiol Biotechnol 106 4445-4458 (2022)
  29. Phosphorylation of pyridoxal 5'-phosphate enzymes: an intriguing and neglected topic. Rossignoli G, Phillips RS, Astegno A, Menegazzi M, Voltattorni CB, Bertoldi M. Amino Acids 50 205-215 (2018)

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  1. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, Ishihara A, Kashyap PC, Fraser JS, Fischbach MA. Cell Host Microbe 16 495-503 (2014)
  2. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons. Canetta S, Bolkan S, Padilla-Coreano N, Song LJ, Sahn R, Harrison NL, Gordon JA, Brown A, Kellendonk C. Mol Psychiatry 21 956-968 (2016)
  3. Activity-dependent regulation of inhibition via GAD67. Lau CG, Murthy VN. J Neurosci 32 8521-8531 (2012)
  4. Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operon. De Biase D, Pennacchietti E. Mol Microbiol 86 770-786 (2012)
  5. Identification of glutamic acid decarboxylase gene and distribution of GABAergic nervous system in the planarian Dugesia japonica. Nishimura K, Kitamura Y, Umesono Y, Takeuchi K, Takata K, Taniguchi T, Agata K. Neuroscience 153 1103-1114 (2008)
  6. Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic clusters. Kanaani J, Kolibachuk J, Martinez H, Baekkeskov S. J Cell Biol 190 911-925 (2010)
  7. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases. Giardina G, Montioli R, Gianni S, Cellini B, Paiardini A, Voltattorni CB, Cutruzzolà F. Proc Natl Acad Sci U S A 108 20514-20519 (2011)
  8. Structure and function of sphingosine-1-phosphate lyase, a key enzyme of sphingolipid metabolism. Bourquin F, Riezman H, Capitani G, Grütter MG. Structure 18 1054-1065 (2010)
  9. Redox-switch modulation of human SSADH by dynamic catalytic loop. Kim YG, Lee S, Kwon OS, Park SY, Lee SJ, Park BJ, Kim KJ. EMBO J 28 959-968 (2009)
  10. How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state. Giardina G, Brunotti P, Fiascarelli A, Cicalini A, Costa MG, Buckle AM, di Salvo ML, Giorgi A, Marani M, Paone A, Rinaldo S, Paiardini A, Contestabile R, Cutruzzolà F. FEBS J 282 1225-1241 (2015)
  11. TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and insulin resistance in muscle cells. Hussey SE, Liang H, Costford SR, Klip A, DeFronzo RA, Sanchez-Avila A, Ely B, Musi N. Biosci Rep 33 37-47 (2012)
  12. In vivo knockdown of GAD67 in the amygdala disrupts fear extinction and the anxiolytic-like effect of diazepam in mice. Heldt SA, Mou L, Ressler KJ. Transl Psychiatry 2 e181 (2012)
  13. A common structural basis for pH- and calmodulin-mediated regulation in plant glutamate decarboxylase. Gut H, Dominici P, Pilati S, Astegno A, Petoukhov MV, Svergun DI, Grütter MG, Capitani G. J Mol Biol 392 334-351 (2009)
  14. Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase. Komori H, Nitta Y, Ueno H, Higuchi Y. J Biol Chem 287 29175-29183 (2012)
  15. Thermal hyperalgesia via supraspinal mechanisms in mice lacking glutamate decarboxylase 65. Kubo K, Nishikawa K, Ishizeki J, Hardy-Yamada M, Yanagawa Y, Saito S. J Pharmacol Exp Ther 331 162-169 (2009)
  16. COOH-terminal clustering of autoantibody and T-cell determinants on the structure of GAD65 provide insights into the molecular basis of autoreactivity. Fenalti G, Hampe CS, Arafat Y, Law RH, Banga JP, Mackay IR, Whisstock JC, Buckle AM, Rowley MJ. Diabetes 57 1293-1301 (2008)
  17. ScanNet: an interpretable geometric deep learning model for structure-based protein binding site prediction. Tubiana J, Schneidman-Duhovny D, Wolfson HJ. Nat Methods 19 730-739 (2022)
  18. Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis. Liu P, Ge X, Ding H, Jiang H, Christensen BM, Li J. J Biol Chem 287 40898-40906 (2012)
  19. A molecular basis for agonist and antagonist actions at GABA(C) receptors. Abdel-Halim H, Hanrahan JR, Hibbs DE, Johnston GA, Chebib M. Chem Biol Drug Des 71 306-327 (2008)
  20. Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade. Crabtree GW, Park AJ, Gordon JA, Gogos JA. Cell Rep 17 570-582 (2016)
  21. Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis. Kass I, Hoke DE, Costa MG, Reboul CF, Porebski BT, Cowieson NP, Leh H, Pennacchietti E, McCoey J, Kleifeld O, Borri Voltattorni C, Langley D, Roome B, Mackay IR, Christ D, Perahia D, Buckle M, Paiardini A, De Biase D, Buckle AM. Proc Natl Acad Sci U S A 111 E2524-9 (2014)
  22. Evidence for GABA-Induced Systemic GABA Accumulation in Arabidopsis upon Wounding. Scholz SS, Malabarba J, Reichelt M, Heyer M, Ludewig F, Mithöfer A. Front Plant Sci 8 388 (2017)
  23. Compartmentalization of GABA synthesis by GAD67 differs between pancreatic beta cells and neurons. Kanaani J, Cianciaruso C, Phelps EA, Pasquier M, Brioudes E, Billestrup N, Baekkeskov S. PLoS One 10 e0117130 (2015)
  24. Extracellular HMGB1 Modulates Glutamate Metabolism Associated with Kainic Acid-Induced Epilepsy-Like Hyperactivity in Primary Rat Neural Cells. Kaneko Y, Pappas C, Malapira T, Vale FĹ, Tajiri N, Borlongan CV. Cell Physiol Biochem 41 947-959 (2017)
  25. C-terminal low-complexity sequence repeats of Mycobacterium smegmatis Ku modulate DNA binding. Kushwaha AK, Grove A. Biosci Rep 33 175-184 (2013)
  26. GABA expression and regulation by sensory experience in the developing visual system. Miraucourt LS, Silva JS, Burgos K, Li J, Abe H, Ruthazer ES, Cline HT. PLoS One 7 e29086 (2012)
  27. Calpain cleavage of brain glutamic acid decarboxylase 65 is pathological and impairs GABA neurotransmission. Buddhala C, Suarez M, Modi J, Prentice H, Ma Z, Tao R, Wu JY. PLoS One 7 e33002 (2012)
  28. Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects. Batista G, Hensch TK. Front Mol Neurosci 12 77 (2019)
  29. Neuroanatomical plasticity in the gonadotropin-releasing hormone system of the ewe: seasonal variation in glutamatergic and gamma-aminobutyric acidergic afferents. Sergeeva A, Jansen HT. J Comp Neurol 515 615-628 (2009)
  30. An analysis of the cross-reactivity of autoantibodies to GAD65 and GAD67 in diabetes. Jayakrishnan B, Hoke DE, Langendorf CG, Buckle AM, Rowley MJ. PLoS One 6 e18411 (2011)
  31. Role of the proteasome in excitotoxicity-induced cleavage of glutamic acid decarboxylase in cultured hippocampal neurons. Baptista MS, Melo CV, Armelão M, Herrmann D, Pimentel DO, Leal G, Caldeira MV, Bahr BA, Bengtson M, Almeida RD, Duarte CB. PLoS One 5 e10139 (2010)
  32. An examination of aspartate decarboxylase and glutamate decarboxylase activity in mosquitoes. Richardson G, Ding H, Rocheleau T, Mayhew G, Reddy E, Han Q, Christensen BM, Li J. Mol Biol Rep 37 3199-3205 (2010)
  33. Editorial Anti-GAD Antibodies and the Cerebellum: Where Do We Stand? Manto M, Mitoma H, Hampe CS. Cerebellum 18 153-156 (2019)
  34. GAD65 as a prototypic autoantigen. Fenalti G, Rowley MJ. J Autoimmun 31 228-232 (2008)
  35. Acute regulation of 5'-AMP-activated protein kinase by long-chain fatty acid, glucose and insulin in rat primary adipocytes. Hebbachi A, Saggerson D. Biosci Rep 33 71-82 (2012)
  36. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase. Burbaeva GSh, Boksha IS, Tereshkina EB, Savushkina OK, Prokhorova TA, Vorobyeva EA. Cerebellum 13 607-615 (2014)
  37. The influence of dietary lipid composition on liver mitochondria from mice following 1 month of calorie restriction. Chen Y, Hagopian K, Bibus D, Villalba JM, López-Lluch G, Navas P, Kim K, McDonald RB, Ramsey JJ. Biosci Rep 33 83-95 (2012)
  38. Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients. Macher S, Zimprich F, De Simoni D, Höftberger R, Rommer PS. Front Immunol 9 2708 (2018)
  39. Characterisation of peptide microarrays for studying antibody-antigen binding using surface plasmon resonance imagery. Nogues C, Leh H, Langendorf CG, Law RH, Buckle AM, Buckle M. PLoS One 5 e12152 (2010)
  40. Expression, immobilization and enzymatic properties of glutamate decarboxylase fused to a cellulose-binding domain. Park H, Ahn J, Lee J, Lee H, Kim C, Jung JK, Lee H, Lee EG. Int J Mol Sci 13 358-368 (2012)
  41. Promoter analysis of the DHCR24 (3β-hydroxysterol Δ(24)-reductase) gene: characterization of SREBP (sterol-regulatory-element-binding protein)-mediated activation. Daimiel LA, Fernández-Suárez ME, Rodríguez-Acebes S, Crespo L, Lasunción MA, Gómez-Coronado D, Martínez-Botas J. Biosci Rep 33 57-69 (2012)
  42. GABAergic system in β-cells: from autoimmunity target to regeneration tool. Fiorina P. Diabetes 62 3674-3676 (2013)
  43. Gamma-aminobutyric acid production using immobilized glutamate decarboxylase followed by downstream processing with cation exchange chromatography. Lee S, Ahn J, Kim YG, Jung JK, Lee H, Lee EG. Int J Mol Sci 14 1728-1739 (2013)
  44. Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome. Rizzi M, Knoth R, Hampe CS, Lorenz P, Gougeon ML, Lemercier B, Venhoff N, Ferrera F, Salzer U, Thiesen HJ, Peter HH, Walker UA, Eibel H. PLoS One 5 e10838 (2010)
  45. Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates. Langendorf CG, Tuck KL, Key TL, Fenalti G, Pike RN, Rosado CJ, Wong AS, Buckle AM, Law RH, Whisstock JC. Biosci Rep 33 137-144 (2013)
  46. Structural determinants of GAD antigenicity. Arafat Y, Fenalti G, Whisstock JC, Mackay IR, Garcia de la Banda M, Rowley MJ, Buckle AM. Mol Immunol 47 493-505 (2009)
  47. A novel homozygous mutation in GAD1 gene described in a schizophrenic patient impairs activity and dimerization of GAD67 enzyme. Magri C, Giacopuzzi E, La Via L, Bonini D, Ravasio V, Elhussiny MEA, Orizio F, Gangemi F, Valsecchi P, Bresciani R, Barbon A, Vita A, Gennarelli M. Sci Rep 8 15470 (2018)
  48. Characterization of CD4+ T cells specific for glutamic acid decarboxylase (GAD65) and proinsulin in a patient with stiff-person syndrome but without type 1 diabetes. Hänninen A, Soilu-Hänninen M, Hampe CS, Deptula A, Geubtner K, Ilonen J, Knip M, Reijonen H. Diabetes Metab Res Rev 26 271-279 (2010)
  49. Crystal structure of non-redox regulated SSADH from Escherichia coli. Ahn JW, Kim YG, Kim KJ. Biochem Biophys Res Commun 392 106-111 (2010)
  50. Identification of the kinetic mechanism of succinyl-CoA synthetase. Li X, Wu F, Beard DA. Biosci Rep 33 145-163 (2013)
  51. Structural characterization of a β-hydroxyacid dehydrogenase from Geobacter sulfurreducens and Geobacter metallireducens with succinic semialdehyde reductase activity. Zhang Y, Zheng Y, Qin L, Wang S, Buchko GW, Garavito RM. Biochimie 104 61-69 (2014)
  52. Ulk4 regulates GABAergic signaling and anxiety-related behavior. Liu M, Fitzgibbon M, Wang Y, Reilly J, Qian X, O'Brien T, Clapcote S, Shen S, Roche M. Transl Psychiatry 8 43 (2018)
  53. De novo assembly and characterization of central nervous system transcriptome reveals neurotransmitter signaling systems in the rice striped stem borer, Chilo suppressalis. Xu G, Wu SF, Wu YS, Gu GX, Fang Q, Ye GY. BMC Genomics 16 525 (2015)
  54. Possible role for glutamic acid decarboxylase in fibromyalgia symptoms: a conceptual model for chronic pain. Fitzgerald CT, Carter LP. Med Hypotheses 77 409-415 (2011)
  55. Crystal structure of Oryza sativa TDC reveals the substrate specificity for TDC-mediated melatonin biosynthesis. Zhou Y, Liao L, Liu X, Liu B, Chen X, Guo Y, Huang C, Zhao Y, Zeng Z. J Adv Res 24 501-511 (2020)
  56. Identification of sites in apolipoprotein A-I susceptible to chymase and carboxypeptidase A digestion. Usami Y, Kobayashi Y, Kameda T, Miyazaki A, Matsuda K, Sugano M, Kawasaki K, Kurihara Y, Kasama T, Tozuka M. Biosci Rep 33 49-56 (2012)
  57. Improving promiscuous mammalian cell entry by the baculovirus Autographa californica multiple nuclear polyhedrosis virus. O'Flynn NM, Patel A, Kadlec J, Jones IM. Biosci Rep 33 23-36 (2012)
  58. Overexpression of Glutamate Decarboxylase in Mesenchymal Stem Cells Enhances Their Immunosuppressive Properties and Increases GABA and Nitric Oxide Levels. Urrutia M, Fernández S, González M, Vilches R, Rojas P, Vásquez M, Kurte M, Vega-Letter AM, Carrión F, Figueroa F, Rojas P, Irarrázabal C, Fuentealba RA. PLoS One 11 e0163735 (2016)
  59. Characterization of continuous B-cell epitopes in the N-terminus of glutamate decarboxylase67 using monoclonal antibodies. Agca S, Houen G, Trier NH. J Pept Sci 20 928-934 (2014)
  60. Discovery of a substrate selectivity motif in amino acid decarboxylases unveils a taurine biosynthesis pathway in prokaryotes. Agnello G, Chang LL, Lamb CM, Georgiou G, Stone EM. ACS Chem Biol 8 2264-2271 (2013)
  61. Function coupling of otoferlin with GAD65 acts to modulate GABAergic activity. Wu W, Rahman MN, Guo J, Roy N, Xue L, Cahill CM, Zhang S, Jia Z. J Mol Cell Biol 7 168-179 (2015)
  62. Similarities between bacterial GAD and human GAD65: Implications in gut mediated autoimmune type 1 diabetes. Bedi S, Richardson TM, Jia B, Saab H, Brinkman FSL, Westley M. PLoS One 17 e0261103 (2022)
  63. Aromatase Derived Estradiol Within the Thalamus Modulates Pain Induced by Varicella Zoster Virus. Kramer PR, Rao M, Stinson C, Bellinger LL, Kinchington PR, Yee MB. Front Integr Neurosci 12 46 (2018)
  64. Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect. Saruta J, To M, Sugimoto M, Yamamoto Y, Shimizu T, Nakagawa Y, Inoue H, Saito I, Tsukinoki K. Int J Mol Sci 18 E1902 (2017)
  65. A downstream process allowing the efficient isolation of a recombinant amphiphilic protein from tobacco leaves. Gecchele E, Schillberg S, Merlin M, Pezzotti M, Avesani L. J Chromatogr B Analyt Technol Biomed Life Sci 960 34-42 (2014)
  66. Purification of L-glutamate decarboxylase from monkey brain. Inoue Y, Ishii K, Miyazaki M, Ueno H. Biosci Biotechnol Biochem 72 2269-2276 (2008)
  67. Role of Met(58) in the regulation of electron/proton transfer in trihaem cytochrome PpcA from Geobacter sulfurreducens. Morgado L, Dantas JM, Simões T, Londer YY, Pokkuluri PR, Salgueiro CA. Biosci Rep 33 11-22 (2012)
  68. The effect of serotonin on GABA synthesis in cultured rat spinal dorsal horn neurons. Wang YY, Legendre P, Huang J, Wang W, Wu SX, Li YQ. J Chem Neuroanat 36 150-159 (2008)
  69. Cry1Aa binding to the cadherin receptor does not require conserved amino acid sequences in the domain II loops. Fujii Y, Tanaka S, Otsuki M, Hoshino Y, Morimoto C, Kotani T, Harashima Y, Endo H, Yoshizawa Y, Sato R. Biosci Rep 33 103-112 (2012)
  70. Enhanced GAD65 production in plants using the MagnICON transient expression system: Optimization of upstream production and downstream processing. Merlin M, Gecchele E, Arcalis E, Remelli S, Brozzetti A, Pezzotti M, Avesani L. Biotechnol J 11 542-553 (2016)
  71. Microbial production of multiple short-chain primary amines via retrobiosynthesis. Kim DI, Chae TU, Kim HU, Jang WD, Lee SY. Nat Commun 12 173 (2021)
  72. Protein-engineered molecules carrying GAD65 epitopes and targeting CD35 selectively down-modulate disease-associated human B lymphocytes. Manoylov IK, Boneva GV, Doytchinova IA, Mihaylova NM, Tchorbanov AI. Clin Exp Immunol 197 329-340 (2019)
  73. Characterization of the bipartite degron that regulates ubiquitin-independent degradation of thymidylate synthase. Barbour KW, Xing YY, Peña EA, Berger FG. Biosci Rep 33 165-173 (2013)
  74. Dietary Supplementation with γ-Aminobutyric Acid Improves Growth, Digestive Enzyme Activity, Non-Specific Immunity and Disease Resistance against Streptococcus iniae in Juvenile Olive Flounder, Paralichthys olivaceus. Farris NW, Hamidoghli A, Bae J, Won S, Choi W, Biró J, Lee S, Bai SC. Animals (Basel) 12 248 (2022)
  75. Electrical hypothesis of toxicity of the Cry toxins for mosquito larvae. Lemeshko VV, Orduz S. Biosci Rep 33 125-136 (2013)
  76. Identification of succinic semialdehyde reductases from Geobacter: expression, purification, crystallization, preliminary functional, and crystallographic analysis. Zhang Y, Gao X, Zheng Y, Garavito RM. Acta Biochim Biophys Sin (Shanghai) 43 996-1002 (2011)
  77. Injecting NMDA and Ro 25-6981 in insular cortex induce neuroplastic changes and neuropathic pain-like behaviour. Yoon MS, Koh CS, Lee J, Shin J, Kong C, Jung HH, Chang JW. Eur J Pain 22 1691-1700 (2018)
  78. Peptide Antibody Reactivity to Homologous Regions in Glutamate Decarboxylase Isoforms and Coxsackievirus B4 P2C. Trier NH, Valdarnini N, Fanelli I, Rovero P, Hansen PR, Schafer-Nielsen C, Ciplys E, Slibinskas R, Pociot F, Friis T, Houen G. Int J Mol Sci 23 4424 (2022)
  79. Abamectin treatment affects glutamate decarboxylase expression and induces higher GABA levels in the citrus red mite, Panonychus citri. Dou W, Xia WK, Niu JZ, Wang JJ. Exp Appl Acarol 72 229-244 (2017)
  80. An Interesting Molecule: γ-Aminobutyric Acid. What Can We Learn from Hydra Polyps? Pierobon P. Brain Sci 11 437 (2021)
  81. Developmental and epileptic encephalopathy 89: A novel bi-allelic variant, molecular dynamics simulation, and a comprehensive clinical and molecular profile. Khorram E, Amini M, Khorrami M. Epilepsia Open 8 571-585 (2023)
  82. Quantum chemistry studies of the catalysis mechanism differences between the two isoforms of glutamic acid decarboxylase. Wang C, Zhu R, Sun H, Li B. J Mol Model 19 705-714 (2013)
  83. The novel P330L pathogenic variant of aromatic amino acid decarboxylase maps on the catalytic flexible loop underlying its crucial role. Bisello G, Kusmierska K, Verbeek MM, Sykut-Cegielska J, Willemsen MAAP, Wevers RA, Szymańska K, Poznanski J, Drozak J, Wertheim-Tysarowska K, Rygiel AM, Bertoldi M. Cell Mol Life Sci 79 305 (2022)
  84. Thermostable D-amino acid decarboxylases derived from Thermotoga maritima diaminopimelate decarboxylase. Marjanovic A, Ramírez-Palacios CJ, Masman MF, Drenth J, Otzen M, Marrink SJ, Janssen DB. Protein Eng Des Sel 34 gzab016 (2021)
  85. A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. Tramonti A, Contestabile R, Florio R, Nardella C, Barile A, Di Salvo ML. Life (Basel) 11 438 (2021)
  86. Increased Production of γ-Aminobutyric Acid from Brewer's Spent Grain Through Bacillus Fermentation. Kim T, Heo S, Na HE, Lee G, Lee JH, Kim JY, Jeong DW. J Microbiol Biotechnol 33 527-532 (2023)
  87. Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamics. Ichise M, Sakoori K, Katayama KI, Morimura N, Yamada K, Ozawa H, Matsunaga H, Hatayama M, Aruga J. Front Mol Neurosci 15 856315 (2022)
  88. MpADC, an L-aspartate-α-decarboxylase, from Myzus persicae, that enables production of β-alanine with high yield by whole-cell enzymatic catalysis. Liu P, Xie S, Guo Q, Chen Y, Fan J, Kumar Nadda A, Huang X, Chu X. Biotechnol Biofuels Bioprod 16 157 (2023)
  89. The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility. Liu X, van Beek N, Cepic A, Andreani NA, Chung CJ, Hermes BM, Yilmaz K, Benoit S, Drenovska K, Gerdes S, Gläser R, Goebeler M, Günther C, von Georg A, Hammers CM, Holtsche MM, Hübner F, Kiritsi D, Schauer F, Linnenmann B, Huilaja L, Tasanen-Määttä K, Vassileva S, Zillikens D, Sadik CD, Schmidt E, Ibrahim S, Baines JF. Front Immunol 14 1212551 (2023)
  90. Two putative glutamate decarboxylases of Streptococcus pneumoniae as possible antigens for the production of anti-GAD65 antibodies leading to type 1 diabetes mellitus. García E. Int Microbiol 26 675-690 (2023)