8JE4

Crystal structure of LimF prenyltransferase (H239G/W273T mutant) bound with the thiodiphosphate moiety of farnesyl S-thiolodiphosphate (FSPP)

8JE4 の概要

• エントリーDOI: 10.2210/pdb8je4/pdb
• 分子名称: prenyltransferase, LimF, MAGNESIUM ION, TRIHYDROGEN THIODIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: ripp, prenylation, abba fold, transferase
• 由来する生物種: Limnothrix sp. CACIAM 69d
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69553.62

構造登録者

Hamada, K.,Oguni, A.,Zhang, Y.,Satake, M.,Goto, Y.,Suga, H.,Ogata, K.,Sengoku, T. (登録日: 2023-05-15, 公開日: 2023-11-08, 最終更新日: 2023-11-22)

主引用文献

Zhang, Y.,Hamada, K.,Satake, M.,Sengoku, T.,Goto, Y.,Suga, H.
Switching Prenyl Donor Specificities of Cyanobactin Prenyltransferases.
J.Am.Chem.Soc., 145:23893-23898, 2023

PubMed Abstract: Prenyltransferases in cyanobactin biosynthesis are of growing interest as peptide alkylation biocatalysts, but their prenylation modes characterized so far have been limited to dimethylallylation (C5) or geranylation (C10). Here we engaged in structure-guided engineering of the prenyl-binding pocket of a His--geranyltransferase LimF to modulate its prenylation mode. Contraction of the pocket by a single mutation led to a His--dimethylallyltransferase. More importantly, pocket expansion by a double mutation successfully repurposed LimF for farnesylation (C15), which is an unprecedented mode in this family. Furthermore, the obtained knowledge of the essential residues to construct the farnesyl-binding pocket has allowed for rational design of a Tyr--farnesyltransferase by a triple mutation of a Tyr--dimethylallyltransferase PagF. These results provide an approach to manipulate the prenyl specificity of cyanobactin prenyltransferases, broadening the chemical space covered by this class of enzymes and expanding the toolbox of peptide alkylation biocatalysts.

PubMed: 37877712
DOI: 10.1021/jacs.3c07373

実験手法

X-RAY DIFFRACTION (2.19 Å)