Structure and function of the acidic amino acid decarboxylase GADL1

Elaheh Mahootchi, Arne Raasakka,‡ Ingeborg Winge,a,b Weisha Luan,c Petri Kursulaa,c* and Jan Haavika,b,d*

a Department of Biomedicine, University of Bergen, Bergen, Norway, b K. G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, c Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland, and d Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

‡ These authors made equal contributions


Glutamic acid decarboxylase-like protein 1 (GADL1) is a recently discovered pyridoxal 5′-phosphate -dependent enzyme that has been associated with lithium response in bipolar disorder. The expression pattern and activity of GADL1 suggest a role in neurotransmitter and neuroprotectant metabolism, notably in the synthesis of beta-alanine and carnosine in the olfactory bulb. The catalytic properties and crystal structure of mouse GADL1 is described, together with a solution model based on small-angle X-ray scattering data.


  • Construct preparation, protein expression and purification
  • Expression and purification of mouse GADL1 (MmGADL1)
  • Crystallization
  • Small-angle X-ray scattering



The substrate specificity and physiological functions of GADL1 are still unclear. While the overall fold and the conformation of the bound PLP are similar to those in other PLP-dependent decarboxylases, GADL1 adopts a more loose conformation in solution, which might have functional relevance in ligand binding and catalysis.


The structure of MmGADL1 and its flexibility in solution, coupled to structural conservation with other PLP-dependent enzymes, point towards functional relevance of these features within the enzyme family. Future work will concentrate on high-resolution structural details of substrate and inhibitor binding by GADL1, as well as characterization of its metabolic role in mouse tissues.


Legg igjen en kommentar

Din e-postadresse vil ikke bli publisert. Obligatoriske felt er merket med *