31JF

Human holo aromatic L-amino acid decarboxylase (AADC) D15G variant native structure

Summary for 31JF

• Entry DOI: 10.2210/pdb31jf/pdb
• Descriptor: Aromatic-L-amino-acid decarboxylase, TETRAETHYLENE GLYCOL (3 entities in total)
• Functional Keywords: plp-dependent transferase, pyridoxal-dependent decarboxylase, aromatic-l-amino-acid decarboxylase, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 54521.72

Authors

Perduca, M.,Bisello, G.,Scapin, V.,Bertoldi, M. (deposition date: 2026-06-08, release date: 2026-11-11)

Primary citation

Bisello, G.,Ucar, S.K.,Yanbolu, A.Y.,Yildirim, C.,Perduca, M.,D'Ambrosio, M.,Franchini, R.,Scapin, V.,Rampini, M.,Bertoldi, M.
Aromatic amino acid decarboxylase - exploring the structural and functional role of its N-terminal domain using deficiency-associated variants.
Febs Lett., 2026

PubMed Abstract: AADC deficiency is a rare autosomal recessive disorder characterized by motor/neurodevelopmental symptoms. Approximately one-third of patients experience recurrent hypoglycemia, with or without neurological involvement. To investigate whether specific variants identified in hypoglycemic patients underlie this metabolic phenotype, we characterized three amino-terminal variants. The crystal structure of p.Asp15Gly revealed disruption of an inter-subunit electrostatic network stabilizing the enzyme interface. Computational analyses predicted that p.Val33Leu and p.Gly36Arg perturb an essential catalytic element. Functional studies showed that p.Asp15Gly retained substantial catalytic activity and coenzyme affinity despite reduced stability, whereas p.Val33Leu and p.Gly36Arg exhibited increasing structural destabilization, reduced coenzyme affinity, and severe catalytic defects. These findings reveal distinct functional roles of the amino-terminal-domain, providing a molecular basis for the clinical variability of AADC deficiency.

PubMed: 42922116
DOI: 10.1002/1873-3468.70490

Experimental method

X-RAY DIFFRACTION (2.13 Å)