3O24

Crystal structure of the brevianamide F prenyltransferase FtmPT1 from Aspergillus fumigatus

3O24 の概要

• エントリーDOI: 10.2210/pdb3o24/pdb
• 関連するPDBエントリー: 3O2K
• 分子名称: Brevianamide F prenyltransferase, SULFATE ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: pt barrel, brevianamide f prenyltransferase, transferase
• 由来する生物種: Aspergillus fumigatus (Sartorya fumigata)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54331.97

構造登録者

Jost, M.,Zocher, G.E.,Stehle, T. (登録日: 2010-07-22, 公開日: 2010-12-08, 最終更新日: 2023-09-06)

主引用文献

Jost, M.,Zocher, G.,Tarcz, S.,Matuschek, M.,Xie, X.,Li, S.M.,Stehle, T.
Structure-function analysis of an enzymatic prenyl transfer reaction identifies a reaction chamber with modifiable specificity.
J.Am.Chem.Soc., 132:17849-17858, 2010

PubMed Abstract: Fungal indole prenyltransferases participate in a multitude of biosynthetic pathways. Their ability to prenylate diverse substrates has attracted interest for potential use in chemoenzymatic synthesis. The fungal indole prenyltransferase FtmPT1 catalyzes the prenylation of brevianamide F in the biosynthesis of fumitremorgin-type alkaloids, which show diverse pharmacological activities and are promising candidates for the development of antitumor agents. Here, we report crystal structures of unliganded Aspergillus fumigatus FtmPT1 as well as of a ternary complex of FtmPT1 bound to brevianamide F and an analogue of its isoprenoid substrate dimethylallyl diphosphate. FtmPT1 assumes a rare α/β-barrel fold, consisting of 10 circularly arranged β-strands surrounded by α-helices. Catalysis is performed in a hydrophobic reaction chamber at the center of the barrel. In combination with mutagenesis experiments, our analysis of the liganded and unliganded structures provides insight into the mechanism of catalysis and the determinants of regiospecificity. Sequence conservation of key features indicates that all fungal indole prenyltransferases possess similar active site architectures. However, while the dimethylallyl diphosphate binding site is strictly conserved in these enzymes, subtle changes in the reaction chamber likely allow for the accommodation of diverse aromatic substrates for prenylation. In support of this concept, we were able to redirect the regioselectivity of FtmPT1 by a single mutation of glycine 115 to threonine. This finding provides support for a potential use of fungal indole prenyltransferases as modifiable bioreactors that can be engineered to catalyze highly specific prenyl transfer reactions.

PubMed: 21105662
DOI: 10.1021/ja106817c

実験手法

X-RAY DIFFRACTION (2.5 Å)