3ALE

A type III polyketide synthase that produces diarylheptanoid

Summary for 3ALE

• Entry DOI: 10.2210/pdb3ale/pdb
• Related: 1CGK 1U0U 3A5Q
• Descriptor: Os07g0271500 protein (2 entities in total)
• Functional Keywords: type iii polyketide synthase, benzalacetone synthase, diarylheptanoid, transferase
• Biological source: Oryza sativa (Rice)
• Total number of polymer chains: 4
• Total formula weight: 179379.97

Authors

Morita, H.,Kato, R.,Sugio, S.,Abe, I. (deposition date: 2010-08-03, release date: 2010-11-03, Last modification date: 2023-11-01)

Primary citation

Morita, H.,Wanibuchi, K.,Nii, H.,Kato, R.,Sugio, S.,Abe, I.
Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa
Proc.Natl.Acad.Sci.USA, 107:19778-19783, 2010

PubMed Abstract: Curcuminoid synthase (CUS) from Oryza sativa is a plant-specific type III polyketide synthase (PKS) that catalyzes the remarkable one-pot formation of the C(6)-C(7)-C(6) diarylheptanoid scaffold of bisdemethoxycurcumin, by the condensation of two molecules of 4-coumaroyl-CoA and one molecule of malonyl-CoA. The crystal structure of O. sativa CUS was solved at 2.5-Å resolution, which revealed a unique, downward expanding active-site architecture, previously unidentified in the known type III PKSs. The large active-site cavity is long enough to accommodate the two C(6)-C(3) coumaroyl units and one malonyl unit. Furthermore, the crystal structure indicated the presence of a putative nucleophilic water molecule, which forms hydrogen bond networks with Ser351-Asn142-H(2)O-Tyr207-Glu202, neighboring the catalytic Cys174 at the active-site center. These observations suggest that CUS employs unique catalytic machinery for the one-pot formation of the C(6)-C(7)-C(6) scaffold. Thus, CUS utilizes the nucleophilic water to terminate the initial polyketide chain elongation at the diketide stage. Thioester bond cleavage of the enzyme-bound intermediate generates 4-coumaroyldiketide acid, which is then kept within the downward expanding pocket for subsequent decarboxylative condensation with the second 4-coumaroyl-CoA starter, to produce bisdemethoxycurcumin. The structure-based site-directed mutants, M265L and G274F, altered the substrate and product specificities to accept 4-hydroxyphenylpropionyl-CoA as the starter to produce tetrahydrobisdemethoxycurcumin. These findings not only provide a structural basis for the catalytic machinery of CUS but also suggest further strategies toward expanding the biosynthetic repertoire of the type III PKS enzymes.

PubMed: 21041675
DOI: 10.1073/pnas.1011499107

Experimental method

X-RAY DIFFRACTION (2.5 Å)