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Crystal structure of (+)-δ-cadinene synthase from Gossypium arboreum and evolutionary divergence of metal binding motifs for catalysis

Gennadios, Heather A., Gonzalez, Veronica, Di Costanzo, Luigi, Li, Amang, Yu, Fanglei, Miller, David James, Allemann, Rudolf Konrad and Christianson, David W. 2009. Crystal structure of (+)-δ-cadinene synthase from Gossypium arboreum and evolutionary divergence of metal binding motifs for catalysis. Biochemistry 48 (26) , pp. 6175-6183. 10.1021/bi900483b

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Abstract

(+)-δ-Cadinene synthase (DCS) from Gossypium arboreum (tree cotton) is a sesquiterpene cyclase that catalyzes the cyclization of farnesyl diphosphate in the first committed step of the biosynthesis of gossypol, a phytoalexin that defends the plant from bacterial and fungal pathogens. Here, we report the X-ray crystal structure of unliganded DCS at 2.4 Å resolution and the structure of its complex with three putative Mg2+ ions and the substrate analogue inhibitor 2-fluorofarnesyl diphosphate (2F-FPP) at 2.75 Å resolution. These structures illuminate unusual features that accommodate the trinuclear metal cluster required for substrate binding and catalysis. Like other terpenoid cyclases, DCS contains a characteristic aspartate-rich D307DTYD311 motif on helix D that interacts with Mg2+A and Mg2+C. However, DCS appears to be unique among terpenoid cyclases in that it does not contain the “NSE/DTE” motif on helix H that specifically chelates Mg2+B, which is usually found as the signature sequence (N,D)D(L,I,V)X(S,T)XXXE (boldface indicates Mg2+B ligands). Instead, DCS contains a second aspartate-rich motif, D451DVAE455, that interacts with Mg2+B. In this regard, DCS is more similar to the isoprenoid chain elongation enzyme farnesyl diphosphate synthase, which also contains two aspartate-rich motifs, rather than the greater family of terpenoid cyclases. Nevertheless, the structure of the DCS−2F-FPP complex shows that the structure of the trinuclear magnesium cluster is generally similar to that of other terpenoid cyclases despite the alternative Mg2+B binding motif. Analyses of DCS mutants with alanine substitutions in the D307DTYD311 and D451DVAE455 segments reveal the contributions of these segments to catalysis.

Item Type: Article
Status: Published
Schools: Chemistry
Cardiff Catalysis Institute (CCI)
Subjects: Q Science > QD Chemistry
Publisher: ACS Publications
ISSN: 0006-2960
Last Modified: 28 Jun 2019 02:06
URI: http://orca.cf.ac.uk/id/eprint/5948

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