Gennadios, Heather A., Gonzalez, Veronica, Di Costanzo, Luigi, Li, Amang, Yu, Fanglei, Miller, David James, Allemann, Rudolf Konrad  ORCID: https://orcid.org/0000-0002-1323-8830 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
|
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: | Schools > Chemistry Research Institutes & Centres > Cardiff Catalysis Institute (CCI) |
| Subjects: | Q Science > QD Chemistry |
| Publisher: | ACS Publications |
| ISSN: | 0006-2960 |
| Last Modified: | 02 Mar 2025 14:56 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/5948 |
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