AADC

Aromatic L-amino acid decarboxylase

Score: 0.464 Price: $0.46 Medium Druggability Status: active Wiki: AADC

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 AADC — PDB 1JS3 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.50

Clinical Stage

Approved

Target Class

Enzyme

Safety

0.40

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.85

Safety Profile0.40

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Approved

Therapeutic Areas:

Parkinson's disease Levodopa-responsive movement disorders Neurodegeneration Motor symptom management in Parkinsonism Combination therapy enhancement

Druggability Rationale: AADC is highly druggable (0.90 score) due to its well-defined catalytic active site, proven clinical validation by approved drug carbidopa, and extensive structural characterization with 3 PDB structures at 1.7 Å resolution. The enzyme's established role in Parkinson's disease therapy and availability of high-quality structural data enable rational drug design of competitive inhibitors targeting the pyridoxal-5'-phosphate (PLP) cofactor binding pocket.

Mechanism: Small molecule inhibitor preventing peripheral conversion of levodopa to dopamine

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

Carbidopa (approved) — Parkinson's disease (with levodopa)

Structural Data:

PDB (3) ✓AlphaFold ✓Cryo-EM —

3RBF 3RBL 3RCH

UniProt: A0A3Q8A018

Binding Pocket Analysis:

The active site features a pyridoxal-5'-phosphate (PLP) cofactor binding pocket that serves as the primary interaction site for substrate (levodopa) and inhibitor binding. Structural data from PDB entries (3RBF, 3RBL, 3RCH) at high resolution (1.7 Å) reveal conserved catalytic residues and cofactor coordination geometry, enabling structure-based design of competitive inhibitors with improved potency and selectivity over carbidopa.

🧬 3D Protein Structure

🧬 AADC — PDB 1JS3 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

Peripheral selectivity is the critical challenge—drugs must inhibit AADC in the periphery while minimizing CNS penetration to avoid reducing central dopamine synthesis. AADC has limited isoforms, reducing isoform selectivity complexity, but off-target inhibition of other PLP-dependent enzymes (e.g., DOPA decarboxylase variants, monoamine oxidases) must be carefully evaluated to prevent adverse metabolic effects.