 |
PDBsum entry 3a5r
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
A structure-Based mechanism for benzalacetone synthase from rheum palmatum.
|
|
|
Authors
|
|
H.Morita,
Y.Shimokawa,
M.Tanio,
R.Kato,
H.Noguchi,
S.Sugio,
T.Kohno,
I.Abe.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2010,
107,
669-673.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Benzalacetone synthase (BAS), a plant-specific type III polyketide synthase
(PKS), catalyzes a one-step decarboxylative condensation of malonyl-CoA and
4-coumaroyl-CoA to produce the diketide benzalacetone. We solved the crystal
structures of both the wild-type and chalcone-producing I207L/L208F mutant of
Rheum palmatum BAS at 1.8 A resolution. In addition, we solved the crystal
structure of the wild-type enzyme, in which a monoketide coumarate intermediate
is covalently bound to the catalytic cysteine residue, at 1.6 A resolution. This
is the first direct evidence that type III PKS utilizes the cysteine as the
nucleophile and as the attachment site for the polyketide intermediate. The
crystal structures revealed that BAS utilizes an alternative, novel active-site
pocket for locking the aromatic moiety of the coumarate, instead of the chalcone
synthase's coumaroyl-binding pocket, which is lost in the active-site of the
wild-type enzyme and restored in the I207L/L208F mutant. Furthermore, the
crystal structures indicated the presence of a putative nucleophilic water
molecule which forms hydrogen bond networks with the Cys-His-Asn catalytic
triad. This suggested that BAS employs novel catalytic machinery for the
thioester bond cleavage of the enzyme-bound diketide intermediate and the final
decarboxylation reaction to produce benzalacetone. These findings provided a
structural basis for the functional diversity of the type III PKS enzymes.
|
|
|
|
|
|
|
