3RBL

Crystal structure of Human aromatic L-amino acid decarboxylase (AADC) in the apo form

Summary for 3RBL

• Entry DOI: 10.2210/pdb3rbl/pdb
• Related: 3RBF 3RCH
• Descriptor: aromatic L-amino acid decarboxylase, CHLORIDE ION (2 entities in total)
• Functional Keywords: apo enzyme, apo form, open conformation, open dimer, exposed, conformational change, parkinson, aadc deficiency, ddc, decarboxylase, plp, l-dopa, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 107961.84

Authors

Giardina, G.,Montioli, R.,Gianni, S.,Cellini, B.,Paiardini, A.,Borri Voltattorni, C.,Cutruzzola, F. (deposition date: 2011-03-29, release date: 2011-10-19, Last modification date: 2023-09-13)

Primary citation

Giardina, G.,Montioli, R.,Gianni, S.,Cellini, B.,Paiardini, A.,Voltattorni, C.B.,Cutruzzola, F.
Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases.
Proc.Natl.Acad.Sci.USA, 108:20514-20519, 2011

PubMed Abstract: DOPA decarboxylase, the dimeric enzyme responsible for the synthesis of neurotransmitters dopamine and serotonin, is involved in severe neurological diseases such as Parkinson disease, schizophrenia, and depression. Binding of the pyridoxal-5'-phosphate (PLP) cofactor to the apoenzyme is thought to represent a central mechanism for the regulation of its activity. We solved the structure of the human apoenzyme and found it exists in an unexpected open conformation: compared to the pig kidney holoenzyme, the dimer subunits move 20 Å apart and the two active sites become solvent exposed. Moreover, by tuning the PLP concentration in the crystals, we obtained two more structures with different conformations of the active site. Analysis of three-dimensional data coupled to a kinetic study allows to identify the structural determinants of the open/close conformational change occurring upon PLP binding and thereby propose a model for the preferential degradation of the apoenzymes of Group II decarboxylases.

PubMed: 22143761
DOI: 10.1073/pnas.1111456108

Experimental method

X-RAY DIFFRACTION (3.24 Å)