1ZB6

Co-Crystal Structure of ORF2 an Aromatic Prenyl Transferase from Streptomyces sp. strain cl190 complexed with GSPP and 1,6-dihydroxynaphtalene

Summary for 1ZB6

• Entry DOI: 10.2210/pdb1zb6/pdb
• Related: 1ZCW 1ZDW 1ZDY
• Descriptor: Aromatic prenyltransferase, MAGNESIUM ION, NITRATE ION, ... (6 entities in total)
• Functional Keywords: novel aromatic prenyltransferase barrel fold, pt-barrel, transferase
• Biological source: Streptomyces sp.
• Total number of polymer chains: 1
• Total formula weight: 34354.94

Authors

Kuzuyama, T.,Noel, J.P.,Richard, S.B. (deposition date: 2005-04-07, release date: 2005-06-21, Last modification date: 2024-02-14)

Primary citation

Kuzuyama, T.,Noel, J.P.,Richard, S.B.
Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products.
Nature, 435:983-987, 2005

PubMed Abstract: The anti-oxidant naphterpin is a natural product containing a polyketide-based aromatic core with an attached 10-carbon geranyl group derived from isoprenoid (terpene) metabolism. Hybrid natural products such as naphterpin that contain 5-carbon (dimethylallyl), 10-carbon (geranyl) or 15-carbon (farnesyl) isoprenoid chains possess biological activities distinct from their non-prenylated aromatic precursors. These hybrid natural products represent new anti-microbial, anti-oxidant, anti-inflammatory, anti-viral and anti-cancer compounds. A small number of aromatic prenyltransferases (PTases) responsible for prenyl group attachment have only recently been isolated and characterized. Here we report the gene identification, biochemical characterization and high-resolution X-ray crystal structures of an architecturally novel aromatic PTase, Orf2 from Streptomyces sp. strain CL190, with substrates and substrate analogues bound. In vivo, Orf2 attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide during naphterpin biosynthesis. In vitro, Orf2 catalyses carbon-carbon-based and carbon-oxygen-based prenylation of a diverse collection of hydroxyl-containing aromatic acceptors of synthetic, microbial and plant origin. These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases.

PubMed: 15959519
DOI: 10.1038/nature03668

Experimental method

X-RAY DIFFRACTION (1.95 Å)