 |
PDBsum entry 3k40
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Crystal structure and substrate specificity of drosophila 3,4-Dihydroxyphenylalanine decarboxylase.
|
|
|
Authors
|
|
Q.Han,
H.Ding,
H.Robinson,
B.M.Christensen,
J.Li.
|
|
|
Ref.
|
|
Plos One, 2010,
5,
e8826.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
BACKGROUND: 3,4-Dihydroxyphenylalanine decarboxylase (DDC), also known as
aromatic L-amino acid decarboxylase, catalyzes the decarboxylation of a number
of aromatic L-amino acids. Physiologically, DDC is responsible for the
production of dopamine and serotonin through the decarboxylation of
3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively. In insects,
both dopamine and serotonin serve as classical neurotransmitters,
neuromodulators, or neurohormones, and dopamine is also involved in insect
cuticle formation, eggshell hardening, and immune responses. PRINCIPAL FINDINGS:
In this study, we expressed a typical DDC enzyme from Drosophila melanogaster,
critically analyzed its substrate specificity and biochemical properties,
determined its crystal structure at 1.75 Angstrom resolution, and evaluated the
roles residues T82 and H192 play in substrate binding and enzyme catalysis
through site-directed mutagenesis of the enzyme. Our results establish that this
DDC functions exclusively on the production of dopamine and serotonin, with no
activity to tyrosine or tryptophan and catalyzes the formation of serotonin more
efficiently than dopamine. CONCLUSIONS: The crystal structure of Drosophila DDC
and the site-directed mutagenesis study of the enzyme demonstrate that T82 is
involved in substrate binding and that H192 is used not only for substrate
interaction, but for cofactor binding of drDDC as well. Through comparative
analysis, the results also provide insight into the structure-function
relationship of other insect DDC-like proteins.
|
|
|
|
|
|
|
