3AWJ

Crystal structure of the Huperzia serrata polyketide synthase 1 complexed with CoA-SH

Summary for 3AWJ

• Entry DOI: 10.2210/pdb3awj/pdb
• Related: 3AWK
• Descriptor: Chalcone synthase-like polyketide synthase, COENZYME A, SULFATE ION, ... (4 entities in total)
• Functional Keywords: type iii polyketide synthase, chalcone synthase, transferase
• Biological source: Huperzia serrata (toothed club-moss)
• Total number of polymer chains: 2
• Total formula weight: 88285.64

Authors

Morita, H.,Kondo, S.,Kato, R.,Sugio, S.,Kohno, T.,Abe, I. (deposition date: 2011-03-23, release date: 2011-08-31, Last modification date: 2023-11-01)

Primary citation

Morita, H.,Yamashita, M.,Shi, S.P.,Wakimoto, T.,Kondo, S.,Kato, R.,Sugio, S.,Kohno, T.,Abe, I.
Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase.
Proc.Natl.Acad.Sci.USA, 108:13504-13509, 2011

PubMed Abstract: HsPKS1 from Huperzia serrata is a type III polyketide synthase (PKS) with remarkable substrate tolerance and catalytic potential. Here we present the synthesis of unnatural unique polyketide-alkaloid hybrid molecules by exploiting the enzyme reaction using precursor-directed and structure-based approaches. HsPKS1 produced novel pyridoisoindole (or benzopyridoisoindole) with the 6.5.6-fused (or 6.6.5.6-fused) ring system by the condensation of 2-carbamoylbenzoyl-CoA (or 3-carbamoyl-2-naphthoyl-CoA), a synthetic nitrogen-containing nonphysiological starter substrate, with two molecules of malonyl-CoA. The structure-based S348G mutant not only extended the product chain length but also altered the cyclization mechanism to produce a biologically active, ring-expanded 6.7.6-fused dibenzoazepine, by the condensation of 2-carbamoylbenzoyl-CoA with three malonyl-CoAs. Thus, the basic nitrogen atom and the structure-based mutagenesis enabled additional C─C and C─N bond formation to generate the novel polyketide-alkaloid scaffold.

PubMed: 21825160
DOI: 10.1073/pnas.1107782108

Experimental method

X-RAY DIFFRACTION (2.2 Å)