2h84

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

Structural highlights

2h84 is a 2 chain structure with sequence from Dictyostelium discoideum AX4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PKS1_DICDI Probable polyketide synthase (By similarity). Produces only acylpyrones; in vitro.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.,Austin MB, Saito T, Bowman ME, Haydock S, Kato A, Moore BS, Kay RR, Noel JP Nat Chem Biol. 2006 Sep;2(9):494-502. Epub 2006 Aug 13. PMID:16906151[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Austin MB, Saito T, Bowman ME, Haydock S, Kato A, Moore BS, Kay RR, Noel JP. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase. Nat Chem Biol. 2006 Sep;2(9):494-502. Epub 2006 Aug 13. PMID:16906151 doi:10.1038/nchembio811
  2. Austin MB, Saito T, Bowman ME, Haydock S, Kato A, Moore BS, Kay RR, Noel JP. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase. Nat Chem Biol. 2006 Sep;2(9):494-502. Epub 2006 Aug 13. PMID:16906151 doi:10.1038/nchembio811

2h84, resolution 2.90Å

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OCA