2H84

Crystal Structure of the C-terminal Type III Polyketide Synthase (PKS III) Domain of 'Steely1' (a Type I/III PKS Hybrid from Dictyostelium)

Summary for 2H84

• Entry DOI: 10.2210/pdb2h84/pdb
• Descriptor: Steely1, HEXAETHYLENE GLYCOL (3 entities in total)
• Functional Keywords: thiolase-fold, type iii polyketide synthase, pks, chalcone-stilbene synthase superfamily, type i pks, type i fatty acid synthase, fas, biosynthetic protein, transferase
• Biological source: Dictyostelium discoideum
• Total number of polymer chains: 2
• Total formula weight: 82035.34

Authors

Austin, M.B.,Saito, T.,Bowman, M.E.,Haydock, S.,Kato, A.,Moore, B.S.,Kay, R.R.,Noel, J.P. (deposition date: 2006-06-06, release date: 2006-08-22, Last modification date: 2023-08-30)

Primary citation

Austin, M.B.,Saito, T.,Bowman, M.E.,Haydock, S.,Kato, A.,Moore, B.S.,Kay, R.R.,Noel, J.P.
Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.
Nat.Chem.Biol., 2:494-502, 2006

PubMed Abstract: Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two approximately 3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis.

PubMed: 16906151
DOI: 10.1038/nchembio811

Experimental method

X-RAY DIFFRACTION (2.9 Å)